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Pesquisa : D08.811.913.477 [Categoria DeCS]
Referências encontradas : 269 [refinar]
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[PMID]:29371602
[Au] Autor:Gélinas R; Mailleux F; Dontaine J; Bultot L; Demeulder B; Ginion A; Daskalopoulos EP; Esfahani H; Dubois-Deruy E; Lauzier B; Gauthier C; Olson AK; Bouchard B; Des Rosiers C; Viollet B; Sakamoto K; Balligand JL; Vanoverschelde JL; Beauloye C; Horman S; Bertrand L
[Ad] Endereço:Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, 1200, Belgium.
[Ti] Título:AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
[So] Source:Nat Commun;9(1):374, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Acetilglucosamina/metabolismo
Cardiomegalia/genética
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Transferases de Grupos Nitrogenados/genética
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/deficiência
Acetilglucosamina/farmacologia
Acilação/efeitos dos fármacos
Animais
Animais Recém-Nascidos
Azasserina/farmacologia
Compostos Azo/farmacologia
Cardiomegalia/metabolismo
Cardiomegalia/patologia
Ativação Enzimática/efeitos dos fármacos
Ativadores de Enzimas/farmacologia
Regulação da Expressão Gênica
Glicosilação/efeitos dos fármacos
Ventrículos do Coração/efeitos dos fármacos
Ventrículos do Coração/metabolismo
Ventrículos do Coração/patologia
Masculino
Camundongos
Camundongos Knockout
Miocárdio/patologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/patologia
Transferases de Grupos Nitrogenados/antagonistas & inibidores
Transferases de Grupos Nitrogenados/metabolismo
Norleucina/análogos & derivados
Norleucina/farmacologia
Fosforilação/efeitos dos fármacos
Cultura Primária de Células
Pironas/farmacologia
Ratos
Ratos Wistar
Transdução de Sinais
Tiofenos/farmacologia
Troponina T/genética
Troponina T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (6-diazo-5-oxonorleucine); 0 (A 769662); 0 (Azo Compounds); 0 (Enzyme Activators); 0 (Pyrones); 0 (Thiophenes); 0 (Troponin T); 832C8OV84S (Norleucine); 87299V3Q9W (Azaserine); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.1.16 (Gfpt1 protein, mouse); EC 2.7.11.1 (AMPK alpha2 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02795-4


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[PMID]:28142188
[Au] Autor:Farine L; Jelk J; Choi JY; Voelker DR; Nunes J; Smith TK; Bütikofer P
[Ad] Endereço:Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, 3012, Switzerland.
[Ti] Título:Phosphatidylserine synthase 2 and phosphatidylserine decarboxylase are essential for aminophospholipid synthesis in Trypanosoma brucei.
[So] Source:Mol Microbiol;104(3):412-427, 2017 May.
[Is] ISSN:1365-2958
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phosphatidylethanolamine (PE) and phosphatidylserine (PS) are ubiquitously expressed and metabolically interconnected glycerophospholipids in eukaryotes and prokaryotes. In Trypanosoma brucei, PE synthesis has been shown to occur mainly via the Kennedy pathway, one of the three routes leading to PE synthesis in eukaryotes, while PS synthesis has not been studied experimentally. We now reveal the importance of T. brucei PS synthase 2 (TbPSS2) and T. brucei PS decarboxylase (TbPSD), two key enzymes involved in aminophospholipid synthesis, for trypanosome viability. By using tetracycline-inducible down-regulation of gene expression and in vivo and in vitro metabolic labeling, we found that TbPSS2 (i) is necessary for normal growth of procyclic trypanosomes, (ii) localizes to the endoplasmic reticulum and (iii) represents the unique route for PS formation in T. brucei. In addition, we identified TbPSD as type I PS decarboxylase in the mitochondrion and found that it is processed proteolytically at a WGSS cleavage site into a heterodimer. Down-regulation of TbPSD expression affected mitochondrial integrity in both procyclic and bloodstream form trypanosomes, decreased ATP production via oxidative phosphorylation in procyclic form and affected parasite growth.
[Mh] Termos MeSH primário: Carboxiliases/metabolismo
Transferases de Grupos Nitrogenados/metabolismo
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Descarboxilação
Mitocôndrias/metabolismo
Fosforilação Oxidativa
Fosfatidiletanolaminas/metabolismo
Fosfatidilserinas/metabolismo
Proteínas de Protozoários/metabolismo
Trypanosoma brucei brucei/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphatidylethanolamines); 0 (Phosphatidylserines); 0 (Protozoan Proteins); 39382-08-6 (phosphatidylethanolamine); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.99.- (Ptdss2 protein, mouse); EC 4.1.1.- (Carboxy-Lyases); EC 4.1.1.65 (phosphatidylserine decarboxylase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170530
[Lr] Data última revisão:
170530
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1111/mmi.13637


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[PMID]:28092359
[Au] Autor:Rodrigues MJ; Windeisen V; Zhang Y; Guédez G; Weber S; Strohmeier M; Hanes JW; Royant A; Evans G; Sinning I; Ealick SE; Begley TP; Tews I
[Ad] Endereço:Biological Sciences, University of Southampton, Southampton, UK.
[Ti] Título:Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis.
[So] Source:Nat Chem Biol;13(3):290-294, 2017 Mar.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Substrate channeling has emerged as a common mechanism for enzymatic intermediate transfer. A conspicuous gap in knowledge concerns the use of covalent lysine imines in the transfer of carbonyl-group-containing intermediates, despite their wideuse in enzymatic catalysis. Here we show how imine chemistry operates in the transfer of covalent intermediates in pyridoxal 5'-phosphate biosynthesis by the Arabidopsis thaliana enzyme Pdx1. An initial ribose 5-phosphate lysine imine is converted to the chromophoric I intermediate, simultaneously bound to two lysine residues and partially vacating the active site, which creates space for glyceraldehyde 3-phosphate to bind. Crystal structures show how substrate binding, catalysis and shuttling are coupled to conformational changes around strand ß6 of the Pdx1 (ßα) -barrel. The dual-specificity active site and imine relay mechanism for migration of carbonyl intermediates provide elegant solutions to the challenge of coordinating a complex sequence of reactions that follow a path of over 20 Å between substrate- and product-binding sites.
[Mh] Termos MeSH primário: Lisina/metabolismo
Vitamina B 6/biossíntese
[Mh] Termos MeSH secundário: Proteínas de Arabidopsis/química
Proteínas de Arabidopsis/metabolismo
Lisina/química
Modelos Moleculares
Estrutura Molecular
Transferases de Grupos Nitrogenados/química
Transferases de Grupos Nitrogenados/metabolismo
Vitamina B 6/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 8059-24-3 (Vitamin B 6); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.- (PDX1 protein, Arabidopsis); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2273


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[PMID]:27758869
[Au] Autor:Chanmee T; Ontong P; Izumikawa T; Higashide M; Mochizuki N; Chokchaitaweesuk C; Khansai M; Nakajima K; Kakizaki I; Kongtawelert P; Taniguchi N; Itano N
[Ad] Endereço:From the Department of Molecular Biosciences, Faculty of Life Sciences, and.
[Ti] Título:Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling.
[So] Source:J Biol Chem;291(46):24105-24120, 2016 Nov 11.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), an HBP rate-limiting enzyme, resembled the results of HA overproduction with regard to HIF-1α accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling.
[Mh] Termos MeSH primário: Hexosaminas/biossíntese
Ácido Hialurônico/biossíntese
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Neoplasias Mamárias Experimentais/metabolismo
Proteínas de Neoplasias/metabolismo
Células-Tronco Neoplásicas/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Feminino
Hexosaminas/genética
Ácido Hialurônico/genética
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Neoplasias Mamárias Experimentais/genética
Neoplasias Mamárias Experimentais/patologia
Camundongos
Proteínas de Neoplasias/genética
Células-Tronco Neoplásicas/patologia
Transferases de Grupos Nitrogenados/genética
Transferases de Grupos Nitrogenados/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hexosamines); 0 (Hif1a protein, mouse); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Neoplasm Proteins); 9004-61-9 (Hyaluronic Acid); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.1.16 (Gfpt1 protein, mouse)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161021
[St] Status:MEDLINE


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[PMID]:27586694
[Au] Autor:Pham VH; Maaroufi H; Balg C; Blais SP; Messier N; Roy PH; Otis F; Voyer N; Lapointe J; Chênevert R
[Ad] Endereço:Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie, Université Laval, Québec, Canada. van-hau.pham.1@ulaval.ca.
[Ti] Título:Inhibition of Helicobacter pylori Glu-tRNA amidotransferase by novel analogues of the putative transamidation intermediate.
[So] Source:FEBS Lett;590(19):3335-3345, 2016 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glutaminyl-tRNA in Helicobacter pylori is formed by an indirect route requiring a noncanonical glutamyl-tRNA synthetase and a tRNA-dependent heterotrimeric amidotransferase (AdT) GatCAB. Widespread use of this pathway among prominent human pathogens, and its absence in the mammalian cytoplasm, identify AdT as a target for the development of antimicrobial agents. We present here the inhibitory properties of three dipeptide-like sulfone-containing compounds analogous to the transamidation intermediates, which are competitive inhibitors of AdT with respect to Glu-tRNA . Molecular docking revealed that AdT inhibition by these compounds depends on π-π stacking interactions between their aromatic groups and Tyr81 of the GatB subunit. The properties of these inhibitors indicate that the 3'-terminal adenine of Glu-tRNA plays a major role in binding to the AdT transamidation active site.
[Mh] Termos MeSH primário: Proteínas de Bactérias/antagonistas & inibidores
Dipeptídeos/farmacologia
Inibidores Enzimáticos/farmacologia
Helicobacter pylori/enzimologia
Transferases de Grupos Nitrogenados/antagonistas & inibidores
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Transferases de Grupos Nitrogenados/química
Transferases de Grupos Nitrogenados/metabolismo
Ligação Proteica
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Dipeptides); 0 (Enzyme Inhibitors); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.- (glutamyl-tRNA(Gln) amidotransferase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12380


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[PMID]:27570073
[Au] Autor:Moloughney JG; Kim PK; Vega-Cotto NM; Wu CC; Zhang S; Adlam M; Lynch T; Chou PC; Rabinowitz JD; Werlen G; Jacinto E
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
[Ti] Título:mTORC2 Responds to Glutamine Catabolite Levels to Modulate the Hexosamine Biosynthesis Enzyme GFAT1.
[So] Source:Mol Cell;63(5):811-26, 2016 Sep 01.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Highly proliferating cells are particularly dependent on glucose and glutamine for bioenergetics and macromolecule biosynthesis. The signals that respond to nutrient fluctuations to maintain metabolic homeostasis remain poorly understood. Here, we found that mTORC2 is activated by nutrient deprivation due to decreasing glutamine catabolites. We elucidate how mTORC2 modulates a glutamine-requiring biosynthetic pathway, the hexosamine biosynthesis pathway (HBP) via regulation of expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), the rate-limiting enzyme of the HBP. GFAT1 expression is dependent on sufficient amounts of glutaminolysis catabolites particularly α-ketoglutarate, which are generated in an mTORC2-dependent manner. Additionally, mTORC2 is essential for proper expression and nuclear accumulation of the GFAT1 transcriptional regulator, Xbp1s. Thus, while mTORC1 senses amino acid abundance to promote anabolism, mTORC2 responds to declining glutamine catabolites in order to restore metabolic homeostasis. Our findings uncover the role of mTORC2 in metabolic reprogramming and have implications for understanding insulin resistance and tumorigenesis.
[Mh] Termos MeSH primário: Fibroblastos/metabolismo
Hexosaminas/biossíntese
Complexos Multiproteicos/metabolismo
Transferases de Grupos Nitrogenados/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Proteína 1 de Ligação a X-Box/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Núcleo Celular/metabolismo
Proliferação Celular
Fibroblastos/citologia
Regulação da Expressão Gênica
Glucose/metabolismo
Glutamina/metabolismo
Células HeLa
Homeostase
Seres Humanos
Ácidos Cetoglutáricos/metabolismo
Alvo Mecanístico do Complexo 1 de Rapamicina
Alvo Mecanístico do Complexo 2 de Rapamicina
Metaboloma/genética
Metabolômica
Camundongos
Complexos Multiproteicos/genética
Transferases de Grupos Nitrogenados/genética
Transdução de Sinais
Serina-Treonina Quinases TOR/genética
Proteína 1 de Ligação a X-Box/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hexosamines); 0 (Ketoglutaric Acids); 0 (Multiprotein Complexes); 0 (X-Box Binding Protein 1); 0 (Xbp1 protein, mouse); 0RH81L854J (Glutamine); 8ID597Z82X (alpha-ketoglutaric acid); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.1.16 (Gfpt1 protein, mouse); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160830
[St] Status:MEDLINE


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[PMID]:27500385
[Au] Autor:Zhao L; Rathnayake UM; Dewage SW; Wood WN; Veltri AJ; Cisneros GA; Hendrickson TL
[Ad] Endereço:Department of Chemistry, Wayne State University, Detroit, MI, USA.
[Ti] Título:Characterization of tunnel mutants reveals a catalytic step in ammonia delivery by an aminoacyl-tRNA amidotransferase.
[So] Source:FEBS Lett;590(18):3122-32, 2016 Sep.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Helicobacter pylori Asp-tRNA(A) (sn) /Glu-tRNA(G) (ln) amidotransferase (GatCAB) utilizes an uncommonly hydrophilic, ~ 40 Å ammonia tunnel for ammonia/ammonium transport between isolated active sites. Hydrophilicity of this tunnel requires a distinct ammonia transport mechanism, which hypothetically occurs through a series of deprotonation and protonation steps. To explore the initiation of this relay mechanism, the highly conserved tunnel residue D185 (in the GatA subunit) was enzymatically and computationally investigated by comparing D185A, D185N, and D185E mutant enzymes to wild-type GatCAB. Our results indicate that D185 acts as an acid/base residue, participating directly in catalysis. To our knowledge, this is the first example of acid/base chemistry in a glutamine-dependent amidotransferase ammonia tunnel.
[Mh] Termos MeSH primário: Amônia/metabolismo
Proteínas de Bactérias/metabolismo
Helicobacter pylori/enzimologia
Mutação de Sentido Incorreto
Transferases de Grupos Nitrogenados/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Domínio Catalítico
Simulação de Dinâmica Molecular
Transferases de Grupos Nitrogenados/química
Transferases de Grupos Nitrogenados/genética
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Bacterial Proteins); 7664-41-7 (Ammonia); EC 2.6.- (GatCAB amidotransferase, Helicobacter pylori); EC 2.6.- (Nitrogenous Group Transferases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170512
[Lr] Data última revisão:
170512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160809
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12347


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[PMID]:27456536
[Au] Autor:Kátai E; Pál J; Poór VS; Purewal R; Miseta A; Nagy T
[Ad] Endereço:Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.
[Ti] Título:Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.
[So] Source:J Cell Mol Med;20(12):2269-2277, 2016 Dec.
[Is] ISSN:1582-4934
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:O-linked ß-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H O for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H O -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins.
[Mh] Termos MeSH primário: Acetilglucosamina/metabolismo
Estresse Oxidativo
Proteínas tau/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Imunofluorescência
Glicosilação/efeitos dos fármacos
Seres Humanos
Peróxido de Hidrogênio/toxicidade
N-Acetilglucosaminiltransferases/genética
N-Acetilglucosaminiltransferases/metabolismo
Transferases de Grupos Nitrogenados/genética
Transferases de Grupos Nitrogenados/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Fosforilação/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (tau Proteins); BBX060AN9V (Hydrogen Peroxide); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.6.- (Nitrogenous Group Transferases); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160727
[St] Status:MEDLINE
[do] DOI:10.1111/jcmm.12910


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[PMID]:27044099
[Au] Autor:Sohn M; Ivanova P; Brown HA; Toth DJ; Varnai P; Kim YJ; Balla T
[Ad] Endereço:Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
[Ti] Título:Lenz-Majewski mutations in PTDSS1 affect phosphatidylinositol 4-phosphate metabolism at ER-PM and ER-Golgi junctions.
[So] Source:Proc Natl Acad Sci U S A;113(16):4314-9, 2016 Apr 19.
[Is] ISSN:1091-6490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in thePTDSS1gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.
[Mh] Termos MeSH primário: Anormalidades Múltiplas/enzimologia
Doenças do Desenvolvimento Ósseo/enzimologia
Membrana Celular/enzimologia
Retículo Endoplasmático/enzimologia
Complexo de Golgi/enzimologia
Deficiência Intelectual/enzimologia
Mutação
Transferases de Grupos Nitrogenados/metabolismo
Fosfatos de Fosfatidilinositol/metabolismo
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/genética
Doenças do Desenvolvimento Ósseo/genética
Membrana Celular/genética
Retículo Endoplasmático/genética
Complexo de Golgi/genética
Células HEK293
Seres Humanos
Deficiência Intelectual/genética
Antígenos de Histocompatibilidade Menor
Transferases de Grupos Nitrogenados/genética
Fosfatos de Fosfatidilinositol/genética
Fosfotransferases (Aceptor do Grupo Álcool)/genética
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Minor Histocompatibility Antigens); 0 (Phosphatidylinositol Phosphates); 0 (phosphatidylinositol 4-phosphate); EC 2.6.- (Nitrogenous Group Transferases); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.67 (phosphatidylinositol phosphate 4-kinase); EC 2.7.8.- (phospholipid serine base exchange enzyme)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160405
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1525719113


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[PMID]:26976271
[Au] Autor:Pham VH; Maaroufi H; Levesque RC; Lapointe J
[Ad] Endereço:Département de Biochimie, de Microbiologie et de Bio-informatique, Faculté des Sciences et de Génie, Université Laval, Québec G1V 0A6, Canada; Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec G1V 0A6, Canada; The Quebec Network for Research on Protein Function, Struc
[Ti] Título:Cyclic peptides identified by phage display are competitive inhibitors of the tRNA-dependent amidotransferase of Helicobacter pylori.
[So] Source:Peptides;79:8-15, 2016 05.
[Is] ISSN:1873-5169
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Helicobacter pylori, the heterotrimeric tRNA-dependent amidotransferase (GatCAB) is essential for protein biosynthesis because it catalyzes the conversion of misacylated Glu-tRNA(Gln) and Asp-tRNA(Asn) into Gln-tRNA(Gln) and Asn-tRNA(Asn), respectively. In this study, we used a phage library to identify peptide inhibitors of GatCAB. A library displaying loop-constrained heptapeptides was used to screen for phages binding to the purified GatCAB. To optimize the probability of obtaining competitive inhibitors of GatCAB with respect to its substrate Glu-tRNA(Gln), we used that purified substrate in the biopanning process of the phage-display technique to elute phages bound to GatCAB at the third round of the biopanning process. Among the eluted phages, we identified several that encode cyclic peptides rich in Trp and Pro that inhibit H. pylori GatCAB in vitro. Peptides P10 and P9 were shown to be competitive inhibitors of GatCAB with respect to its substrate Glu-tRNA(Gln), with Ki values of 126 and 392µM, respectively. The docking models revealed that the Trp residues of these peptides form π-π stacking interactions with Tyr81 of the synthetase active site, as does the 3'-terminal A76 of tRNA, supporting their competitive behavior with respect to Glu-tRNA(Gln) in the transamidation reaction. These peptides can be used as scaffolds in the search for novel antibiotics against the pathogenic bacteria that require GatCAB for Gln-tRNA(Gln) and/or Asn-tRNA(Asn) formation.
[Mh] Termos MeSH primário: Antibacterianos/química
Proteínas de Bactérias/antagonistas & inibidores
Helicobacter pylori/enzimologia
Transferases de Grupos Nitrogenados/antagonistas & inibidores
Peptídeos Cíclicos/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/química
Proteínas de Bactérias/isolamento & purificação
Domínio Catalítico
Cinética
Modelos Moleculares
Transferases de Grupos Nitrogenados/química
Transferases de Grupos Nitrogenados/isolamento & purificação
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Peptides, Cyclic); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.- (glutamyl-tRNA(Gln) amidotransferase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE



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