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https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#1
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28722313/cellular-glycosylation-senses-metabolic-changes-and-modulates-cell-plasticity-during-emt
#2
REVIEW
P Carvalho-Cruz, F Alisson-Silva, A R Todeschini, W B Dias
Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward Hexosamine Biosynthesis Pathway (HBP) which fuels aberrant glycosylation patterns that are extensively observed in cancer cells...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28713921/anti%C3%A2-lung-cancer-effect-of-glucosamine-by-suppressing-the-phosphorylation-of-foxo
#3
Zhanwu Yu, Yinghua Ju, Hongxu Liu
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710799/high-glucose-induces-o-glcnac-glycosylation-of-the-vitamin-d-receptor-vdr-in-thp1-cells-and-in-human-macrophages-derived-from-monocytes
#4
Fernando Hernandez-Sánchez, Silvia Guzmán-Beltrán, María Teresa Herrera, Yolanda Gonzalez, Manuel Salgado, Guadalupe Fabian, Martha Torres
Chronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP-GlcNAc. UDP-GlcNAc is the sugar donor for the enzyme-mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR)...
July 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28691313/moderate-mammalian-target-of-rapamycin-inhibition-induces-autophagy-in-htr8-svneo-cells-via-o-linked-%C3%AE-n-acetylglucosamine-signaling
#5
Qiuxia Zhang, Quan Na, Weiwei Song
AIM: Autophagy, a highly regulated process with a dual role (pro-survival or pro-death), has been implicated in adverse pregnancy outcomes. The aim of this study was to explore the mechanism whereby mammalian target of rapamycin (mTOR) signaling regulates autophagy by modulating protein O-GlcNAcylation in human trophoblasts. METHODS: HTR8/SVneo cells were incubated in serum-free medium for different time intervals or treated with varying doses of Torin1. Protein expression and cell apoptosis were detected by immunoblotting and flow cytometry, respectively...
July 10, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28688099/increased-o-linked-n-acetylglucosamine-modification-of-nf-%C3%AE-b-and-augmented-cytokine-production-in-the-placentas-from-hyperglycemic-rats
#6
Vanessa Dela Justina, Jéssica S Gonçalves, Raiany Alves de Freitas, Adriany Dias Fonseca, Gustavo T Volpato, Rita C Tostes, Fernando S Carneiro, Victor Vitorino Lima, Fernanda R Giachini
Inflammation as a result of NF-κB activation may result from the classical (canonical) pathway, with disconnection of the IκB inhibitor and subsequent nuclear translocation or, alternatively, by post-translational modifications of modulatory proteins or NF-κB subunits (non-canonical pathway). We hypothesized that hyperglycemia-induced increased glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) of NF-κB in placental tissue leads to augmented production of pro-inflammatory cytokines, culminating in placental dysfunction and fetal restriction growth...
July 8, 2017: Inflammation
https://www.readbyqxmd.com/read/28686627/wga-based-lectin-affinity-gel-electrophoresis-a-novel-method-for-the-detection-of-o-glcnac-modified-proteins
#7
Yuji Kubota, Ko Fujioka, Mutsuhiro Takekawa
Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. Here, we describe a novel method in which O-GlcNAcylated and non-O-GlcNAcylated forms of proteins are separated by lectin affinity gel electrophoresis using wheat germ agglutinin (WGA), which primarily binds to N-acetylglucosamine residues...
2017: PloS One
https://www.readbyqxmd.com/read/28681591/o-glcnacylation-of-nf-kappab-promotes-lung-metastasis-of-cervical-cancer-cells-via-upregulation-of-cxcr4-expression
#8
Akhtar Ali, Sung Hwan Kim, Min Jun Kim, Mee Young Choi, Sang Soo Kang, Gyeong Jae Cho, Yoon Sook Kim, Jun-Young Choi, Wan Sung Choi
C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. NF-kappaB regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-kappaB promotes its transcriptional activity. Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-kappaB in lung metastasis of cervical cancer. We found elevated levels of O-linked-Nactylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-kappaB p65 (p65) and CXCR4 in cervical cancer cells...
July 6, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28670495/bitterness-in-sugar-o-glcnacylation-aggravates-pre-b-acute-lymphocytic-leukemia-through-glycolysis-via-the-pi3k-akt-c-myc-pathway
#9
Bing Zhang, Panpan Zhou, Xue Li, Qing Shi, Dong Li, Xiuli Ju
Abnormal cellular energetics has emerged as a hallmark of cancer cells. Deregulating aerobic glycolysis can alter multiple metabolic and signaling pathways in cancer cells, and trigger unlimited growth and proliferation. Accumulating evidence suggests that elevated levels of protein modification with β-N-acetylglucosamine (O-GlcNAcylation) along with dysregulation of O-GlcNAc transferase (OGT) and/or O-GlcNAcase (OGA) levels may act as a nutrient sensor in cancer cells. However, the underlying mechanism of O-GlcNAcylation and the relationship between O-GlcNAcylation and glycolysis are largely unknown in pre-B acute lymphocytic leukemia (pre-B-ALL)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28669142/polymorphism-in-the-intron-20-of-porcine-o-linked-n-acetylglucosamine-transferase
#10
Jong Gug Kim, Dan Nonneman, Doo-Wan Kim, Sangsu Shin, Gary A Rohrer
OBJECTIVE: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes the addition of O-GlcNAc and GlcNAcylation has extensive crosstalk with phosphorylation to regulate signaling and transcription. Pig OGT is located near the region of chromosome X that affects follicle stimulating hormone level and testes size. The objective of this study was to find the variations of OGT between European and Chinese pigs. METHODS: Pigs were tested initially for polymorphism in OGT among European and Chinese pigs by polymerase chain reaction and sequencing at the U...
August 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28663241/glycosylation-of-keap1-links-nutrient-sensing-to-redox-stress-signaling
#11
Po-Han Chen, Timothy J Smith, Jianli Wu, Priscila F Siesser, Brittany J Bisnett, Farhan Khan, Maxwell Hogue, Erik Soderblom, Flora Tang, Jeffrey R Marks, Michael B Major, Benjamin M Swarts, Michael Boyce, Jen-Tsan Chi
O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets...
June 29, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28661453/lxr%C3%AE-regulates-hepatic-chrebp%C3%AE-activity-and-lipogenesis-upon-glucose-but-not-fructose-feeding-in-mice
#12
Qiong Fan, Rikke C Nørgaard, Christian Bindesbøll, Christin Lucas, Knut Tomas Dalen, Eshrat Babaie, Harri M Itkonen, Jason Matthews, Hilde I Nebb, Line M Grønning-Wang
Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis. LXRα/β double knockout (LXRα(-/-)/β(-/-)) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis. However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown...
June 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28659383/recognition-of-a-glycosylation-substrate-by-the-o-glcnac-transferase-tpr-repeats
#13
Karim Rafie, Olawale Raimi, Andrew T Ferenbach, Vladimir S Borodkin, Vaibhav Kapuria, Daan M F van Aalten
O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28657654/quantitative-proteomics-identifies-altered-o-glcnacylation-of-structural-synaptic-and-memory-associated-proteins-in-alzheimer-s-disease
#14
Sheng Wang, Feng Yang, Vladislav A Petyuk, Anil K Shukla, Matthew E Monroe, Marina A Gritsenko, Karin D Rodland, Richard D Smith, Wei-Jun Qian, Cheng-Xin Gong, Tao Liu
Protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease, however detailed molecular characterization of this important protein posttranslational modification at proteome level has been highly challenging, due to its low stoichiometry and labile nature. Herein we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in post-mortem human brain tissues with and without Alzheimer's disease using isobaric tandem mass tags labeling, chemoenzymatic photocleavage enrichment and liquid chromatography coupled to mass spectrometry...
June 28, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28642969/diverse-metabolic-effects-of-o-glcnacylation-in-the-pancreas-but-limited-effects-in-insulin-sensitive-organs-in-mice
#15
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
AIMS/HYPOTHESIS: O-GlcNAcylation is characterised by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) and serves in sensing intracellular nutrients by modulating various cellular processes. Although it has been speculated that O-GlcNAcylation is associated with glucose metabolism, its exact role in whole body glucose metabolism has not been fully elucidated. Here, we investigated whether loss of O-GlcNAcylation globally and in specific organs affected glucose metabolism in mammals under physiological conditions...
June 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28637651/pivotal-role-of-o-glcnac-modification-in-cold-induced-thermogenesis-by-brown-adipose-tissue-through-mitochondrial-biogenesis
#16
Natsuko Ohashi, Katsutaro Morino, Shogo Ida, Osamu Sekine, Mengistu Lemecha, Shinji Kume, Shi-Young Park, Cheol Soo Choi, Satoshi Ugi, Hiroshi Maegawa
Adipose tissues considerably influence metabolic homeostasis, and both white (WAT) and brown adipose tissue (BAT) play significant roles in lipid and glucose metabolism. O-GlcNAc modification is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (Ogt), subsequently modulating various cellular processes. However, little is known about the role of O-GlcNAc modification in adipose tissues. Here, we report the critical role of O-GlcNAc modification in cold-induced thermogenesis...
June 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#17
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28627871/the-sulfur-linked-analogue-of-o-glcnac-s-glcnac-is-an-enzymatically-stable-and-reasonable-structural-surrogate-for-o-glcnac-at-the-peptide-and-protein-levels
#18
Cesar A De Leon, Paul M Levine, Timothy W Craven, Matthew R Pratt
Synthetic proteins bearing site-specific posttranslational modifications have revolutionized our understanding of their biological functions in vitro and in vivo. One such modification, O-GlcNAcylation, is the dynamic addition of β-N-acetyl glucosamine to the side chains of serine and threonine residues of proteins, yet our understanding of the site-specific impact of O-GlcNAcylation remains difficult to evaluate in vivo because of the potential for enzymatic removal by endogenous O-GlcNAcase (OGA). Thioglycosides are generally perceived to be enzymatically stable structural mimics of O-GlcNAc; however, in vitro experiments with small-molecule GlcNAc thioglycosides have demonstrated that OGA can hydrolyze these linkages, indicating that S-linked β-N-acetyl glucosamine (S-GlcNAc) on peptides or proteins may not be completely stable...
June 30, 2017: Biochemistry
https://www.readbyqxmd.com/read/28625484/nuclear-factor-erythroid-2-related-transcription-factor-1-nrf1-is-regulated-by-o-glcnac-transferase
#19
Jeong Woo Han, Joshua L Valdez, Daniel V Ho, Candy S Lee, Hyun Min Kim, Xiaorong Wang, Lan Huang, Jefferson Y Chan
The Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability...
June 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28624365/o-glcnacylation-of-amyloid-%C3%AE-precursor-protein-at-threonine-576-residue-regulates-trafficking-and-processing
#20
Yoon Sun Chun, Oh-Hoon Kwon, Sungkwon Chung
The pathological hallmark of Alzheimer's disease (AD) is associated with the accumulation of amyloid-β (Aβ) derived from proteolytic processing of amyloid-β precursor protein (APP). APP undergoes post-translational modification including N- and O-glycosylation. O-GlcNAcylation is a novel type of O-glycosylation, mediated by O-GlcNAc transferase attaching O-β-N-acetylglucosamine (O-GlcNAc) to serine/threonine residues of the target proteins. O-GlcNAc is removed by O-GlcNAcase. We have previously reported that increasing O-GlcNAcylated APP using the O-GlcNAcase inhibitor, PUGNAc, increases its trafficking rate to the plasma membrane and decreases its endocytosis rate, resulting in decreased Aβ production...
August 19, 2017: Biochemical and Biophysical Research Communications
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