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https://www.readbyqxmd.com/read/30515991/amyloid-%C3%AE-induced-elevation-of-o-glcnacylated-c-fos-promotes-neuronal-cell-death
#1
Heesun Choi, Chaeyoung Kim, Hyundong Song, Moon-Yong Cha, Hyun Jin Cho, Sung Min Son, Haeng Jun Kim, Inhee Mook-Jung
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive memory loss resulting from cumulative neuronal cell death. O-linked β-N-acetyl glucosamine (O-GlcNAc) modification of the proteins reflecting glucose metabolism is altered in the brains of patients with AD. However, the link between altered O-GlcNAc modification and neuronal cell death in AD is poorly understood. Here, we examined the regulation of O-GlcNAcylation of c-Fos and the effects of O-GlcNAcylated c-Fos on neuronal cell death during AD pathogenesis...
December 4, 2018: Aging Cell
https://www.readbyqxmd.com/read/30515357/model-based-in-silico-analysis-of-the-pi3k-akt-pathway-the-elucidation-of-cross-talk-between-diabetes-and-breast-cancer
#2
Sammia Rehman, Ayesha Obaid, Anam Naz, Amjad Ali, Shahzina Kanwal, Jamil Ahmad
Background: A positive association between diabetes and breast cancer has been identified by various epidemiological and clinical studies. However, the possible molecular interactions between the two heterogeneous diseases have not been fully determined yet. There are several underlying mechanisms which may increase the risk of breast cancer in diabetic patients. Introduction: In this study, we focused on the role of O-GlcNAc transferase (OGT) enzyme in the regulation of phosphatidylinositol-3 kinase (PI3K) pathway through activation/deactivation of Akt protein...
2018: PeerJ
https://www.readbyqxmd.com/read/30504766/adipocyte-ogt-governs-diet-induced-hyperphagia-and-obesity
#3
Min-Dian Li, Nicholas B Vera, Yunfan Yang, Bichen Zhang, Weiming Ni, Enida Ziso-Qejvanaj, Sheng Ding, Kaisi Zhang, Ruonan Yin, Simeng Wang, Xu Zhou, Ethan X Fang, Tian Xu, Derek M Erion, Xiaoyong Yang
Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity. Whether and how overnutrition increases appetite through the adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues. Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases. Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake...
November 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/30504378/effects-of-global-o-glcnacylation-on-galectin-gene-expression-profiles-in-human-cancer-cell-lines
#4
Ali A Sherazi, Komal A Jariwala, Amanda N Cybulski, Justin W Lewis, Jim Karagiannis, Robert C Cumming, Alexander V Timoshenko
BACKGROUND/AIM: The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines. MATERIALS AND METHODS: Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction...
December 2018: Anticancer Research
https://www.readbyqxmd.com/read/30467790/chemical-characterization-of-the-milk-oligosaccharides-of-some-artiodactyla-species-including-giraffe-giraffa-camelopardalis-sitatunga-tragelaphus-spekii-deer-cervus-nippon-yesoensis-and-water-buffalo-bubalus-bubalis
#5
Yuri Mineguchi, Midori Miyoshi, Epi Taufik, Ayumi Kawamura, Takuya Asakawa, Isao Suzuki, Kousaku Souma, Michiko Okubo, Tadao Saito, Kenji Fukuda, Sadaki Asakuma, Tadasu Urashima
Mammalian milk/colostrum usually contains oligosaccharides along with the predominant disaccharide lactose. It has been found that the number and identity of these milk oligosaccharides varies among mammalian species. Oligosaccharides predominate over lactose in the milk/colostrum of Arctoidea species (Carnivora), whereas lactose predominates over milk oligosaccharides in Artiodactyla including cow, sheep, goat, camel, reindeer and pig. To clarify whether heterogeneity of a variety of milk oligosaccharides is found within other species of Artiodactyla, they were studied in the milk of giraffe, sitatunga, deer and water buffalo...
December 2018: Glycoconjugate Journal
https://www.readbyqxmd.com/read/30464755/o-glcnac-as-an-integrator-of-signaling-pathways
#6
REVIEW
Qunxiang Ong, Weiping Han, Xiaoyong Yang
O-GlcNAcylation is an important posttranslational modification governed by a single pair of enzymes-O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). These two enzymes mediate the dynamic cycling of O-GlcNAcylation on a wide variety of cytosolic, nuclear and mitochondrial proteins in a nutrient- and stress-responsive fashion. While cellular functions of O-GlcNAcylation have been emerging, little is known regarding the precise mechanisms how the enzyme pair senses the environmental cues to elicit molecular and physiological changes...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30462203/a-widely-compatible-expression-system-for-the-production-of-highly-o-glcnacylated-recombinant-protein-in-escherichia-coli
#7
Hong Gao, Minghui Shi, Ruihong Wang, Chaojie Wang, Changlun Shao, Yuchao Gu, Wengong Yu
O-GlcNAcylation is a ubiquitous and dynamic post-translational modification on serine/threonine residues of nucleocytoplasmic proteins in metazoa, which plays a critical role in numerous physiological and pathological processes. But the O-GlcNAcylation on most proteins is often substoichiometric, which hinders the functional study of the O-GlcNAcylation. This study aimed to improve the production of highly O-GlcNAcylated recombinant proteins in Escherichia coli (E. coli). To achieve this goal, we constructed a bacterial artificial chromosome-based chloramphenicol-resistant expression vector co-expressing O-GlcNAc transferase (OGT) and key enzymes (phosphoglucose mutase, GlmM and N-acetylglucosamine-1-phosphate uridyltransferase, GlmU) of the uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis pathway in E...
December 1, 2018: Glycobiology
https://www.readbyqxmd.com/read/30459710/a-novel-glycoproteomics-workflow-reveals-dynamic-o-glcnacylation-of-cop%C3%AE-1-as-a-candidate-regulator-of-protein-trafficking
#8
Nathan J Cox, Peter M Luo, Timothy J Smith, Brittany J Bisnett, Erik J Soderblom, Michael Boyce
O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration. Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it. However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30459708/involvement-of-o-glcnacylation-in-the-skeletal-muscle-physiology-and-physiopathology-focus-on-muscle-metabolism
#9
REVIEW
Matthias Lambert, Bruno Bastide, Caroline Cieniewski-Bernard
Skeletal muscle represents around 40% of whole body mass. The principal function of skeletal muscle is the conversion of chemical energy toward mechanic energy to ensure the development of force, provide movement and locomotion, and maintain posture. This crucial energy dependence is maintained by the faculty of the skeletal muscle for being a central place as a "reservoir" of amino acids and carbohydrates in the whole body. A fundamental post-translational modification, named O-GlcNAcylation, depends, inter alia , on these nutrients; it consists to the transfer or the removal of a unique monosaccharide (N-acetyl-D-glucosamine) to a serine or threonine hydroxyl group of nucleocytoplasmic and mitochondrial proteins in a dynamic process by the O-GlcNAc Transferase (OGT) and the O-GlcNAcase (OGA), respectively...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30455348/glucosamine-improves-survival-in-a-mouse-model-of-sepsis-and-attenuates-sepsis-induced-lung-injury-and-inflammation
#10
Ji-Sun Hwang, Kyung-Hong Kim, Jiwon Park, Sang-Min Kim, Hyeongjin Cho, Yunkyoung Lee, Inn-Oc Han
The aim of the current study was to investigate the effects of glucosamine (GlcN) on septic lethality and sepsis-induced inflammation using animal models of mice and zebrafish. GlcN pretreatment improved survival in the cecal ligation and puncture (CLP)-induced sepsis mouse model and attenuated LPS-induced septic lung injury and systemic inflammation. GlcN suppressed LPS-induced M1-specific but not M2-specific gene expression. Furthermore, increased expressions of inflammatory genes in visceral tissue of LPS-injected zebrafish were suppressed by GlcN...
November 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30446550/identification-and-characterization-of-a-glcnac-de-n-acetylase-from-the-hyperthermophilic-archaeon-sulfolobus-solfataricus
#11
Roberta Iacono, Andrea Strazzulli, Luisa Maurelli, Nicola Curci, Angela Casillo, Maria Michela Corsaro, Marco Moracci, Beatrice Cobucci-Ponzano
Sulfolobus solfataricus is an aerobic crenarchael hyperthermophile with optimum growth at T>80°C and pH 2-4. Within the crenarchaeal group of Sulfolobales, N -acetyl-glucosamine (GlcNAc) has been shown to be a component of exopolysaccharides (EPS), forming their biofilms, and of the N -glycan decorating some proteins. The metabolism of GlcNAc is still poorly understood in Archaea and one approach to gaining information on that is through the identification and functional characterization of carbohydrate active enzymes (CAZymes) involved in the modification of GlcNAc...
November 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/30444036/o-glcnac-induced-nuclear-translocation-of-hnrnp-k-is-associated-with-progression-and-metastasis-of-cholangiocarcinoma
#12
Chatchai Phoomak, Dayoung Park, Atit Silsirivanit, Kanlayanee Sawanyawisuth, Kulthida Vaeteewoottacharn, Marutpong Detarya, Chaisiri Wongkham, Carlito B Lebrilla, Wongkham Sopit
O-GlcNAcylation is a key post-translational modification that modifies the functions of proteins. Associations between O-GlcNAcylation, shorter survival of cholangiocarcinoma (CCA) patients and increased migration/invasion of CCA cell lines have been reported. However, the specific O-GlcNAcylated proteins (OGPs) that participate in promotion of CCA progression are poorly understood. OGPs were isolated from human CCA cell lines, KKU-213 and KKU-214, using a click chemistry-based enzymatic labeling system, identified using LC-MS/MS, and searched against an OGP database...
November 15, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/30429311/insights-into-the-roles-of-cmk-1-and-ogt-1-in-interstimulus-interval-dependent-habituation-in-caenorhabditis-elegans
#13
Evan L Ardiel, Troy A McDiarmid, Tiffany A Timbers, Kirsten C Y Lee, Javad Safaei, Steven L Pelech, Catharine H Rankin
Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner...
November 14, 2018: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/30427586/the-fine-art-of-destruction-a-guide-to-in-depth-glycoproteomic-analyses-exploiting-the-diagnostic-potential-of-fragment-ions
#14
Marcus Hoffmann, Markus Pioch, Alexander Pralow, René Hennig, Robert Kottler, Udo Reichl, Erdmann Rapp
The unambiguous mass spectrometric identification and characterization of glycopeptides is crucial to elucidate the micro- and macroheterogeneity of glycoproteins. Here, we propose combining lower and stepped collisional energy fragmentation for the in-depth and site-specific analysis of N- and O-glycopeptides. Using a set of four representative and biopharmaceutically-relevant glycoproteins (IgG, fibrinogen, lactotransferrin, and ribonuclease B), we highlight the benefits and limitations of the developed workflow and provide a state-of-the-art blueprint for conducting high-quality in-depth N- and O-glycoproteomic analyses...
November 14, 2018: Proteomics
https://www.readbyqxmd.com/read/30412832/novel-glucopyranoside-c2-derived-1-2-3-triazoles-displaying-selective-inhibition-of-o-glcnacase-oga
#15
Michelle O Igual, Paulo S G Nunes, Rafael M da Costa, Susimaire P Mantoani, Rita C Tostes, Ivone Carvalho
O-GlcNAcylation or O-GlcNAc modification is a post-translational modification of several proteins responsible for fundamental cellular processes. Dysregulation of the O-GlcNAc pathway has been linked to the etiology of several diseases such as neurodegenerative and cardiovascular diseases, type 2 diabetes and cancer. O-GlcNAcase (OGA) catalyzes the removal of O-GlcNAc from the modified proteins and several carbohydrate-based OGA inhibitors have been synthesized to understand the role of O-GlcNAc-modified proteins in physiological and pathological conditions...
October 26, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/30412792/diminished-o-glcnacylation-in-alzheimer-s-disease-is-strongly-correlated-with-mitochondrial-anomalies
#16
Tiffany S Pinho, Sónia C Correia, George Perry, António Francisco Ambrósio, Paula I Moreira
Uncover the initial cause(s) underlying Alzheimer's disease (AD) pathology is imperative for the development of new therapeutic interventions to counteract AD-related symptomatology and neuropathology in a timely manner. The early stages of AD are characterized by a brain hypometabolic state as denoted by faulty glucose uptake and utilization and abnormal mitochondrial function and distribution which, ultimately, culminates in synaptic "starvation" and neuronal degeneration. Importantly, it was recently recognized that the post-translational modification β-N-acetylglucosamine (O-GlcNAc) modulates mitochondrial function, motility and distribution being proposed to act as a nutrient sensor that links glucose and the metabolic status to neuronal function...
November 6, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30401951/unravelling-the-role-of-o-glycans-in-influenza-a-virus-infection
#17
Juliane Mayr, Kam Lau, Jimmy C C Lai, Ivan A Gagarinov, Yun Shi, Sarah McAtamney, Renee W Y Chan, John Nicholls, Mark von Itzstein, Thomas Haselhorst
The initial stage of host cell infection by influenza A viruses (IAV) is mediated through interaction of the viral haemagglutinin (HA) with cell surface glycans. The binding requirement of IAVs for Galβ(1,4)Glc/ GlcNAc (lactose/lactosamine) glycans with a terminal α(2,6)-linked (human receptors) or α(2,3)-linked (avian receptors) N-acetylneuraminic residue commonly found on N-glycans, is well-established. However the role and significance of sialylated Galβ(1,3)GalNAc (core 1) epitopes that are typical O-glycoforms in influenza virus pathogenesis remains poorly detailed...
November 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30400201/the-many-ways-by-which-o-glcnacylation-may-orchestrate-the-diversity-of-complex-glycosylations
#18
James Biwi, Christophe Biot, Yann Guerardel, Anne-Sophie Vercoutter-Edouart, Tony Lefebvre
Unlike complex glycosylations, O -GlcNAcylation consists of the addition of a single N -acetylglucosamine unit to serine and threonine residues of target proteins, and is confined within the nucleocytoplasmic and mitochondrial compartments. Nevertheless, a number of clues tend to show that O -GlcNAcylation is a pivotal regulatory element of its complex counterparts. In this perspective, we gather the evidence reported to date regarding this connection. We propose different levels of regulation that encompass the competition for the nucleotide sugar UDP-GlcNAc, and that control the wide class of glycosylation enzymes via their expression, catalytic activity, and trafficking...
November 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30397120/combinatorial-regulation-of-hepatic-cytoplasmic-signaling-and-nuclear-transcriptional-events-by-the-ogt-rev-erb%C3%AE-complex
#19
Alexandre Berthier, Manjula Vinod, Geoffrey Porez, Agata Steenackers, Jérémy Alexandre, Nao Yamakawa, Céline Gheeraert, Maheul Ploton, Xavier Maréchal, Julie Dubois-Chevalier, Agnès Hovasse, Christine Schaeffer-Reiss, Sarah Cianférani, Christian Rolando, Fabrice Bray, Hélène Duez, Jérôme Eeckhoute, Tony Lefebvre, Bart Staels, Philippe Lefebvre
The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα-interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERBα cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERBα ligands mostly affected cytoplasmic OGT activity...
November 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30386294/direct-crosstalk-between-o-glcnacylation-and-phosphorylation-of-tau-protein-investigated-by-nmr-spectroscopy
#20
Gwendoline Bourré, François-Xavier Cantrelle, Amina Kamah, Béatrice Chambraud, Isabelle Landrieu, Caroline Smet-Nocca
The formation of intraneuronal fibrillar inclusions of tau protein is associated with several neurodegenerative diseases referred to as tauopathies including Alzheimer's disease (AD). A common feature of these pathologies is hyperphosphorylation of tau, the main component of fibrillar assemblies such as Paired Helical Filaments (PHFs). O -β-linked N-acetylglucosaminylation ( O -GlcNAcylation) is another important posttranslational modification involved in regulation of tau pathophysiology. Among the benefits of O -GlcNAcylation, modulation of tau phosphorylation levels and inhibition of tau aggregation properties have been described while decreased O -GlcNAcylation could be involved in the raise of tau phosphorylation associated with AD...
2018: Frontiers in Endocrinology
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