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https://www.readbyqxmd.com/read/28526214/high-glucose-environment-induced-intracellular-o-glcnac-glycosylation-and-reduced-galectin-7-expression-in-keratinocytes-implications-on-impaired-diabetic-wound-healing
#1
Shu-Mei Huang, Ching-Shuang Wu, Min-Hsi Chiu, Hui-Jun Yang, Gwo-Shing Chen, Cheng-Che E Lan
BACKGROUND: Diabetes is an important global health issue due to its increasing prevalence and association with various complications. Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition...
April 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28521765/inhibition-of-o-glcnacase-leads-to-elevation-of-o-glcnac-tau-and-reduction-of-tauopathy-and-cerebrospinal-fluid-tau-in-rtg4510-mice
#2
Nicholas B Hastings, Xiaohai Wang, Lixin Song, Brent D Butts, Diane Grotz, Richard Hargreaves, J Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X Lu, Maureen Maguire, Veeravan Mahadomrongkul, Ernest J McEachern, Xuesong Ouyang, Thomas W Rosahl, Harold Selnick, Michaela Stanton, Giuseppe Terracina, David J Vocadlo, Ganfeng Wang, Joseph L Duffy, Eric M Parker, Lili Zhang
BACKGROUND: Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models...
May 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28515473/placental-o-glcnac-transferase-expression-and-interactions-with-the-glucocorticoid-receptor-are-sex-specific-and-regulated-by-maternal-corticosterone-exposure-in-mice
#3
Marie Pantaleon, Sarah E Steane, Kathryn McMahon, James S M Cuffe, Karen M Moritz
Maternal stress programs offspring disease in a sexually dimorphic manner with males often more adversely affected. Previous studies of maternal glucocorticoid exposure suggest male vulnerability may derive from placental alterations. The hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are part of an essential adaptive survival response in healthy cells. The key enzyme involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently identified as a sex-specific placental biomarker of maternal stress...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514044/specific-identification-of-glycoproteins-bearing-the-tn-antigen-in-human-cells
#4
Jiangnan Zheng, Haopeng Xiao, Ronghu Wu
Glycoproteins contain a wealth of valuable information regarding the development and disease status of cells. In cancer cells, some glycans (such as the Tn antigen) are highly up-regulated, but this remains largely unknown for glycoproteins with a particular glycan. Herein, an innovative method combining enzymatic and chemical reactions was first designed to enrich glycoproteins with the Tn antigen. Using synthetic glycopeptides with O-GalNAc (the Tn antigen) or O-GlcNAc, we demonstrated that the method is selective for glycopeptides with O-GalNAc and can distinguish between these two modifications...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28510447/synthesis-of-a-highly-azide-reactive-and-thermosensitive-biofunctional-reagent-for-efficient-enrichment-and-large-scale-identification-of-o-glcnac-proteins-by-mass-spectrometry
#5
Wanjun Zhang, Tong Liu, Hangyan Dong, Haihong Bai, Fang Tian, Zhaomei Shi, Mingli Chen, Jianhua Wang, Weijie Qin, Xiaohong Qian
O-linked β-N-acetylglucosamine (O-GlcNAc) is a ubiquitous post-translational modification of proteins in eukaryotic cells. Despite their low abundance, O-GlcNAc-modified proteins play many important roles in regulating gene expression, signal transduction, and cell cycle. Aberrant O-GlcNAc proteins are correlated with many major human diseases, such as Alzheimer's disease, diabetes, and cancer. Because of the extremely low stoichiometry of O-GlcNAc proteins, enrichment is required before mass spectrometry analysis for large-scale identification and in-depth understanding of their cellular function...
May 16, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28502704/ketogenic-diet-leads-to-o-glcnac-modification-in-the-btbr-t-tf-j-mouse-model-of-autism
#6
Christopher Newell, Virginia L Johnsen, Nellie C Yee, Warren J Xu, Matthias S Klein, Aneal Khan, Jong M Rho, Jane Shearer
BACKGROUND: Protein O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a post-translational modification to Ser/Thr residues that integrates energy supply with demand. Abnormal O-GlcNAc patterning is evident in several neurological disease states including epilepsy, Alzheimer's disease and autism spectrum disorder (ASD). A potential treatment option for these disorders includes the high-fat, low-carbohydrate, ketogenic diet (KD). The goal of this study was to determine whether the KD induces changes in O-GlcNAc in the BTBR(T+tf/j) (BTBR) mouse model of ASD...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28499244/microrna-24-1-suppresses-mouse-hepatoma-cell-invasion-and-metastasis-via-directly-targeting-o-glcnac-transferase
#7
Yubo Liu, Huang Huang, Meijun Liu, Qiong Wu, Wenli Li, Jianing Zhang
MicroRNAs (miRNAs) are endogenous non-coding regulatory RNAs involved in multiple cellular processes. Emerging evidences showed that miRNAs are involved in changing the cell surface glycosylation modification and oncogenesis. In this study, the role of miRNA-24-1 in O-GlcNAcylation and metastasis of mouse hepatocarcinoma cells was investigated. miRNAs expression array profiles were obtained from mouse hepatocarcinoma cell lines Hca-P and Hca-F with the low/high lymphatic metastasis potential, respectively. Based on the miRNAs expression array profiles, miRNA-24-1 expression was found to exhibit converse coincidence with metastasis potential, O-GlcNAc transferase (OGT) expression and O-GlcNAcylation...
May 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28488703/protein-o-glcnacylation-emerging-mechanisms-and-functions
#8
REVIEW
Xiaoyong Yang, Kevin Qian
O-GlcNAcylation - the attachment of O-linked N-acetylglucosamine (O-GlcNAc) moieties to cytoplasmic, nuclear and mitochondrial proteins - is a post-translational modification that regulates fundamental cellular processes in metazoans. A single pair of enzymes - O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) - controls the dynamic cycling of this protein modification in a nutrient- and stress-responsive manner. Recent years have seen remarkable advances in our understanding of O-GlcNAcylation at levels that range from structural and molecular biology to cell signalling and gene regulation to physiology and disease...
May 10, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28488246/potential-coordination-role-between-o-glcnacylation-and-epigenetics
#9
REVIEW
Donglu Wu, Yong Cai, Jingji Jin
Dynamic changes of the post-translational O-GlcNAc modification (O-GlcNAcylation) are controlled by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the glycoside hydrolase O-GlcNAcase (OGA) in cells. O-GlcNAcylation often occurs on serine (Ser) and threonine (Thr) residues of the specific substrate proteins via the addition of O-GlcNAc group by OGT. It has been known that O-GlcNAcylation is not only involved in many fundamental cellular processes, but also plays an important role in cancer development through various mechanisms...
May 9, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28487326/xbp1-x-box-binding-protein-1-dependent-o-glcnacylation-is-neuroprotective-in-ischemic-stroke-in-young-mice-and-its-impairment-in-aged-mice-is-rescued-by-thiamet-g
#10
Meng Jiang, Shu Yu, Zhui Yu, Huaxin Sheng, Ying Li, Shuai Liu, David S Warner, Wulf Paschen, Wei Yang
BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)...
May 9, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28487126/o-glcnac-modification-inhibits-the-calpain-mediated-cleavage-of-%C3%AE-synuclein
#11
Paul M Levine, Cesar A De Leon, Ana Galesic, Aaron Balana, Nicholas P Marotta, Yuka E Lewis, Matthew R Pratt
The major protein associated with Parkinson's disease (PD) is α-synuclein, as it can form toxic amyloid-aggregates that are a hallmark of many neurodegenerative diseases. α-Synuclein is a substrate for several different posttranslational modifications (PTMs) that have the potential to affect its biological functions and/or aggregation. However, the biophysical effects of many of these modifications remain to be established. One such modification is the addition of the monosaccharide N-acetyl-glucosamine, O-GlcNAc, which has been found on several α-synuclein serine and threonine residues in vivo...
April 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28481368/regulation-of-mir-483-3p-by-the-o-linked-n-acetylglucosamine-transferase-links-chemosensitivity-to-glucose-metabolism-in-liver-cancer-cells
#12
F Pepe, S Pagotto, S Soliman, C Rossi, P Lanuti, C Braconi, R Mariani-Costantini, R Visone, A Veronese
The miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3/PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28481247/epigenetic-bases-of-aberrant-glycosylation-in-cancer
#13
REVIEW
Fabio Dall'Olio, Marco Trinchera
In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as "glycogenes". The extreme complexity of the glycome requires the regulatory layer to be provided by the epigenetic mechanisms. Almost all types of cancers present glycosylation aberrations, giving rise to phenotypic changes and to the expression of tumor markers. In this review, we discuss how cancer-associated alterations of promoter methylation, histone methylation/acetylation, and miRNAs determine glycomic changes associated with the malignant phenotype...
May 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28474822/in-vitro-biochemical-assays-for-o-glcnac-processing-enzymes
#14
Eun Ju Kim
O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are the only enzymes that regulate the dynamics of protein O-GlcNAcylation. Protein O-GlcNAcylation is an important post-translational modification (PTM) of nuclear and cytoplasmic proteins with O-linked ß-N-acetyl-glucosamine (O-GlcNAc). O-GlcNAc and its enzymes are involved in a wide variety of cellular processes and are linked to the pathological progression of chronic diseases. Considering their emerging biological significance, systematic and rapid methods to determine the activities of OGT and OGA have become essential and several chemical/biochemical methods for measuring these enzymes' activities have been developed...
May 5, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28474680/the-essential-role-of-yap-o-glcnacylation-in-high-glucose-stimulated-liver-tumorigenesis
#15
Xiao Zhang, Yongxia Qiao, Qi Wu, Yan Chen, Shaowu Zou, Xiangfan Liu, Guoqing Zhu, Yinghui Zhao, Yuxin Chen, Yongchun Yu, Qiuhui Pan, Jiayi Wang, Fenyong Sun
O-GlcNAcylation has been implicated in the tumorigenesis of various tissue origins, but its function in liver tumorigenesis is not clear. Here, we demonstrate that O-GlcNAcylation can enhance the expression, stability and function of Yes-associated protein (YAP), the downstream transcriptional regulator of the Hippo pathway and a potent oncogenic factor in liver cancer. O-GlcNAcylation induces transformative phenotypes of liver cancer cells in a YAP-dependent manner. An O-GlcNAc site of YAP was identified at Thr241, and mutating this site decreased the O-GlcNAcylation, stability, and pro-tumorigenic capacities of YAP, while increasing YAP phosphorylation...
May 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28470537/erratum-to-o-glcnac-glycosylation-of-nnos-promotes-neuronal-apoptosis-following-glutamate-excitotoxicity
#16
Rongrong Chen, Peipei Gong, Tao Tao, Yilu Gao, Jianhong Shen, Yaohua Yan, Chengwei Duan, Jun Wang, Xiaojuan Liu
No abstract text is available yet for this article.
May 3, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28455227/suppression-of-ogt-by-microrna24-reduces-foxa1-stability-and-prevents-breast-cancer-cells-invasion
#17
Yubo Liu, Huang Huang, Yu Cao, Qiong Wu, Wenli Li, Jianing Zhang
O-GlcNAc transferase (OGT) catalyzes the addition of O-GlcNAc to certain serine or threonine residue on a wide variety of cytosolic and nuclear proteins and regulates cellular activities such as signaling and transcription. Although there are emerging evidences that OGT plays important roles in breast cancer metastasis, the underlying mechanism is not fully understood. In this study, we demonstrated that up-regulation of OGT correlates with breast cancer cells invasion. Over-expression of OGT stimulates cells invasion, while OGT silence exhibits the opposite effects...
April 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28450392/o-linked-n-acetylglucosamine-transferase-1-regulates-global-histone-h4-acetylation-via-stabilization-of-the-non-specific-lethal-protein-nsl3
#18
Dong-Lu Wu, Lin-Hong Zhao, Zhi-Tong Feng, Chao Yu, Jian Ding, Ling-Yao Wang, Fei Wang, Da Liu, Hui-Hui Zhu, Fei-Yang Xing, Joan W Conaway, Ronald C Conaway, Yong Cai, Jing-Ji Jin
The human MOF-containing histone acetyltransferase (HAT) NSL (non-specific lethal) complex comprises 9 subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase (isoform 1) (OGT1). However, whether O-GlcNAc transferase activity of OGT1 controls HAT activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remains unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4K16, K5, and K8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3...
April 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28427939/nrage-induces-%C3%AE-catenin-arm-o-glcnacylation-and-negatively-regulates-wnt-signaling
#19
Yuxin Chen, Lei Jin, Bin Xue, Dong Jin, Fenyong Sun, Chuanjun Wen
The Wnt pathway is crucial for animal development, as well as tumor formation. Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427012/label-free-electrochemical-biosensing-of-small-molecule-inhibition-on-o-glcnac-glycosylation
#20
Yu Yang, Yuxin Gu, Bin Wan, Xiaomin Ren, Liang-Hong Guo
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter...
September 15, 2017: Biosensors & Bioelectronics
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