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[PMID]:28607489
[Au] Autor:Wang H; Nicolay BN; Chick JM; Gao X; Geng Y; Ren H; Gao H; Yang G; Williams JA; Suski JM; Keibler MA; Sicinska E; Gerdemann U; Haining WN; Roberts TM; Polyak K; Gygi SP; Dyson NJ; Sicinski P
[Ad] Endereço:Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
[Ti] Título:The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival.
[So] Source:Nature;546(7658):426-430, 2017 06 15.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. This re-directs the glycolytic intermediates into the pentose phosphate (PPP) and serine pathways. Inhibition of cyclin D3-CDK6 in tumour cells reduces flow through the PPP and serine pathways, thereby depleting the antioxidants NADPH and glutathione. This, in turn, increases the levels of reactive oxygen species and causes apoptosis of tumour cells. The pro-survival function of cyclin D-associated kinase operates in tumours expressing high levels of cyclin D3-CDK6 complexes. We propose that measuring the levels of cyclin D3-CDK6 in human cancers might help to identify tumour subsets that undergo cell death and tumour regression upon inhibition of CDK4 and CDK6. Cyclin D3-CDK6, through its ability to link cell cycle and cell metabolism, represents a particularly powerful oncoprotein that affects cancer cells at several levels, and this property can be exploited for anti-cancer therapy.
[Mh] Termos MeSH primário: Ciclina D3/metabolismo
Quinase 6 Dependente de Ciclina/metabolismo
Neoplasias/metabolismo
Neoplasias/patologia
[Mh] Termos MeSH secundário: Aminopiridinas/farmacologia
Aminopiridinas/uso terapêutico
Animais
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Quinase 4 Dependente de Ciclina/antagonistas & inibidores
Quinase 4 Dependente de Ciclina/metabolismo
Quinase 6 Dependente de Ciclina/antagonistas & inibidores
Feminino
Glicólise/efeitos dos fármacos
Seres Humanos
Camundongos
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
Estresse Oxidativo/efeitos dos fármacos
Via de Pentose Fosfato/efeitos dos fármacos
Fosfofrutoquinase-1/metabolismo
Fosforilação/efeitos dos fármacos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimologia
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
Purinas/farmacologia
Purinas/uso terapêutico
Piruvato Quinase/metabolismo
Espécies Reativas de Nitrogênio/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Serina/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aminopyridines); 0 (Cyclin D3); 0 (Purines); 0 (Reactive Nitrogen Species); 0 (Reactive Oxygen Species); 452VLY9402 (Serine); EC 2.7.1.11 (Phosphofructokinase-1); EC 2.7.1.40 (Pyruvate Kinase); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (CDK6 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4); EC 2.7.11.22 (Cyclin-Dependent Kinase 6); TK8ERE8P56 (ribociclib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1038/nature22797


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[PMID]:28545955
[Au] Autor:Ismail R; Ul Hussain M
[Ad] Endereço:Department of Biotechnology, Hazratbal Srinagar, University of Kashmir, Jammu and Kashmir, India.
[Ti] Título:The up regulation of phosphofructokinase1 (PFK1) protein during chemically induced hypoxia is mediated by the hypoxia-responsive internal ribosome entry site (IRES) element, present in its 5'untranslated region.
[So] Source:Biochimie;139:38-45, 2017 Aug.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Astrocytes cope-up the hypoxia conditions by up regulating the activity of the enzymes catalyzing the irreversible steps of the glycolytic pathway. The phosphofructokinase1 (PFK1), which converts fructose-6-phosphate to fructose-1, 6-bisphosphate, is the major regulatory enzyme of the glycolytic pathway. For this purpose, we investigated the expression regulation of the PFK1 during chemically induced hypoxia. PRINCIPAL RESULT: After 48 h of the chemically induced hypoxia induction of the C6 glioma cells, the PFK1 protein depicted strong up regulation, with no appreciable change in its mRNA levels. The di-cistronic assay indicated the presence of a weak internal ribosome entry site (IRES) element in the 5'UTR of the PFK1 mRNA. Interestingly, the weak IRES element of the PFK1 was strongly up regulated after 48 h of the chemically induced hypoxia, indicative of a possible mechanism responsible for the induction of the PFK1 protein. The authenticity of the hypoxia-regulated IRES element of the PFK1, relative to the presence of the cryptic promoter element and/or the cryptic splicing was established using promoterless di-cistronic assay and the RT-PCR analysis. Moreover, the ectopic expression of the polypyrimidine tract binding (PTB) protein resulted in the enhanced activity of the IRES element of the PFK1. Additionally, it was established that the chemically induced hypoxia resulted in the increased shuttling of the PTB from the cell nucleus to the cytosol. MAJOR CONCLUSION: The presence of a hypoxia responsive IRES element, in the 5'UTR of the PFK1 was established to be the possible mechanism responsible for the up regulation of the PFK1 protein. Our data provides an interesting mechanism that may explain the increased glycolytic capacity of the astrocytes after brain hypoxia.
[Mh] Termos MeSH primário: Regiões 5´ não Traduzidas/genética
Glioma/metabolismo
Hipóxia/metabolismo
Sítios Internos de Entrada Ribossomal/genética
Fosfofrutoquinase-1/metabolismo
Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Western Blotting
Cobalto/toxicidade
Frutosefosfatos
Glioma/genética
Glioma/patologia
Hipóxia/induzido quimicamente
Hipóxia/genética
Fosfofrutoquinase-1/genética
Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética
Regiões Promotoras Genéticas/genética
RNA Mensageiro/genética
Ratos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Ativação Transcricional
Células Tumorais Cultivadas
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5' Untranslated Regions); 0 (Fructosephosphates); 0 (Internal Ribosome Entry Sites); 0 (RNA, Messenger); 139076-35-0 (Polypyrimidine Tract-Binding Protein); 3G0H8C9362 (Cobalt); 6814-87-5 (fructose-6-phosphate); EC 2.7.1.11 (Phosphofructokinase-1); EVS87XF13W (cobaltous chloride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE


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[PMID]:28073995
[Au] Autor:Xin Y; Zhou J; Ding Q; Chen C; Wu X; Wang X; Wang H; Jiang X
[Ad] Endereço:Department of Laboratory Medicine, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
[Ti] Título:A pericentric inversion of chromosome X disrupting and resulting in haemophilia A.
[So] Source:J Clin Pathol;70(8):656-661, 2017 Aug.
[Is] ISSN:1472-4146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIMS: The frequency of X chromosome pericentric inversion is much less than that of autosome chromosome. We hereby characterise a pericentric inversion of X chromosome associated with severe factor VIII (FVIII) deficiency in a sporadic haemophilia A (HA) pedigree. METHODS: PCR primer walking and genome walking strategies were adopted to identify the exact breakpoints of the inversion. Copy number variations (CNVs) of the and the whole chromosomes were detected by AccuCopy and Affymetrix CytoScan High Definition (HD) assays, respectively. A karyotype analysis was performed by cytogenetic G banding technique. RESULTS: We identified a previously undescribed type of pericentric inversion of the X chromosome [inv(X)(p11.21q28)] in the proband with FVIII:C <1%. One breakpoint was located in the intron 7 of the 8, which disrupted the transcription of the and the other located in the upstream of the of the X chromosome. The inversion segment was approximately 64.4% of the total chromosomal length. The karyotype analysis of the X chromosome confirmed the pericentric inversion of the X chromosome in the proband and his mother. A haplotype analysis traced the inversion to his maternal grandfather, who was not a somatic mosaic of the inversion. This finding indicated that the causative mutation may originate from his germ cells or a rare possibility of germ-cell mosaicism. CONCLUSIONS: The characterisation of pericentric inversion involving extended the molecular mechanisms causing HA. The pericentric inversion rearrangement involves by non-homologous end joining is responsible for pathogensis of severe HA.
[Mh] Termos MeSH primário: Inversão Cromossômica/genética
Fator VIII/genética
Hemofilia A/genética
Mutação/genética
[Mh] Termos MeSH secundário: Pré-Escolar
Pontos de Quebra do Cromossomo
Cromossomos Humanos X
Éxons/genética
Estudo de Associação Genômica Ampla
Genótipo
Seres Humanos
Cariótipo
Masculino
Linhagem
Fosfofrutoquinase-1/genética
RNA Mensageiro/genética
Transcrição Genética/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (F8 protein, human); 0 (RNA, Messenger); 9001-27-8 (Factor VIII); EC 2.7.1.11 (Phosphofructokinase-1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1136/jclinpath-2016-204050


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[PMID]:28049690
[Au] Autor:Miyazawa H; Yamaguchi Y; Sugiura Y; Honda K; Kondo K; Matsuda F; Yamamoto T; Suematsu M; Miura M
[Ad] Endereço:Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
[Ti] Título:Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching.
[So] Source:Development;144(1):63-73, 2017 01 01.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development.
[Mh] Termos MeSH primário: Membrana Corioalantoide/embriologia
Membrana Corioalantoide/metabolismo
Metabolismo Energético/genética
Frutose-Bifosfato Aldolase/genética
Glucose/metabolismo
Fosfofrutoquinase-1/genética
[Mh] Termos MeSH secundário: Animais
Embrião de Mamíferos
Desenvolvimento Embrionário/genética
Feminino
Frutose-Bifosfato Aldolase/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Regulação Enzimológica da Expressão Gênica
Glicólise/genética
Troca Materno-Fetal/genética
Redes e Vias Metabólicas/genética
Camundongos
Camundongos Endogâmicos ICR
Camundongos Transgênicos
Fosfofrutoquinase-1/metabolismo
Gravidez
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lin-28 protein, mouse); 0 (RNA-Binding Proteins); EC 2.7.1.11 (Phosphofructokinase-1); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1242/dev.138545


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[PMID]:27858215
[Au] Autor:Herrera M; Herves MA; Giráldez I; Skar K; Mogren H; Mortensen A; Puvanendran V
[Ad] Endereço:IFAPA Centro Agua del Pino, El Rompido-Punta Umbría rd, 21450, Cartaya, Spain. marcelino.herrera@juntadeandalucia.es.
[Ti] Título:Effects of amino acid supplementations on metabolic and physiological parameters in Atlantic cod (Gadus morhua) under stress.
[So] Source:Fish Physiol Biochem;43(2):591-602, 2017 Apr.
[Is] ISSN:1573-5168
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The effects of tryptophan (Trp) and phenylalanine (Phe) diet supplementation on the stress and metabolism of the Atlantic cod have been studied. Fish were fed diet supplemented with Trp or Phe or control diet for 1 week. At the end of the feeding trial, fish were subjected to air exposure or heat shock. Following samples of blood, liver and muscle were taken from the fish and were analyzed for stress and metabolic indicators. After an air exposure, plasma cortisol levels in fish fed with Trp and Phe diets were lower compared to the fish fed the control diet. Diets containing both amino acids increased significantly the liver transaminase activities in juvenile cod. During thermal stress, high Trp contents had significant effects on fructose biphosphatase activity though Phe did not. Overall, activities of glucose 6-phosphate dehydrogenase, pyruvate kinase, and phosphofructokinase increased significantly for both amino acid diets. For the thermal stress, fish had the highest values of those activities for the 3Trp diet. Trp content in the diet had significant effects on the transaminase activity in muscle during air stress compared to fish fed control and Phe diets. Muscle alanine transaminase activity for thermal stress in fish fed any diet was not significantly different from the control. Both Trp and Phe supplementations reduced the stress markers in the cod; hence, they could be used as additives for the stress attenuation. However, they also raised the activity of key enzymes in glycolysis and gluconeogenesis, mainly the Trp diets.
[Mh] Termos MeSH primário: Suplementos Nutricionais
Gadus morhua
Fenilalanina/farmacologia
Estresse Fisiológico/efeitos dos fármacos
Triptofano/farmacologia
[Mh] Termos MeSH secundário: Ar
Alanina Transaminase/metabolismo
Animais
Aspartato Aminotransferases/metabolismo
Glicemia/análise
Proteínas de Peixes/metabolismo
Frutose-Bifosfatase/metabolismo
Gadus morhua/sangue
Gadus morhua/metabolismo
Gadus morhua/fisiologia
Glucosefosfato Desidrogenase/metabolismo
Temperatura Alta
Hidrocortisona/sangue
Ácido Láctico/sangue
Fígado/efeitos dos fármacos
Fígado/metabolismo
Músculos/efeitos dos fármacos
Músculos/metabolismo
Fosfofrutoquinase-1/metabolismo
Piruvato Quinase/metabolismo
Estresse Fisiológico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Fish Proteins); 33X04XA5AT (Lactic Acid); 47E5O17Y3R (Phenylalanine); 8DUH1N11BX (Tryptophan); EC 1.1.1.49 (Glucosephosphate Dehydrogenase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 2.7.1.11 (Phosphofructokinase-1); EC 2.7.1.40 (Pyruvate Kinase); EC 2.7.1.56 (1-phosphofructokinase); EC 3.1.3.11 (Fructose-Bisphosphatase); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1007/s10695-016-0314-3


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[PMID]:27723463
[Au] Autor:Xia B; Wang L; Nie L; Zhou Q; Huang X
[Ad] Endereço:State Key Laboratory of Food Science and Technology, School of Environment and Civil Engineering, Jiangsu Key Laboratory of Anaerobic Biotechnology, Jiangnan University, Wuxi 214122, China; Jiangsu Cooperative Innovation Center of Water Treatment Technology and Materials, Suzhou University of Scienc
[Ti] Título:A pathway of bisphenol A affecting mineral element contents in plant roots at different growth stages.
[So] Source:Ecotoxicol Environ Saf;135:115-122, 2017 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bisphenol A (BPA), an environmental endocrine disruptor, is an important industrial raw material. The wide use of BPA has increased the risk of BPA release into the environment, and it has become a new environmental pollutant. In this work, the ecological deleterious effects of this new pollutant on soybean roots at different growth stages were investigated by determining the contents of mineral elements (P, K, Ca, and Mg) and analyzing root activity and the activities of critical respiratory enzymes (hexokinase, phosphofructokinase, pyruvate kinase, and isocitrate dehydrogenase). Our results revealed that low dose (1.5mg/L) of BPA increased the levels of P, K, Mg, and Ca in soybean roots at different growth stages. Whereas, high doses (6.0 and 12.0mg/L) of BPA decreased the levels of P, K, and Mg contents in a dose-dependent manner. BPA had a promotive effect on the content of Ca in soybean roots. Synchronous observation showed that the aforementioned dual response to BPA were also observed in the root activity and respiratory enzyme activities. The effects of BPA on the mineral element contents, root activity and respiratory enzyme activities in soybean roots at different growth stages followed the order: flowering and podding stage>seed-filling stage>seedling stage (mineral element contents); seedling stage>flowering and podding stage>seed-filling stage (root activity and respiratory enzyme activities). In a word, the response of plant root activity and respiratory enzyme activities to BPA pollution is a pathway of BPA affecting mineral element contents in plant roots.
[Mh] Termos MeSH primário: Compostos Benzidrílicos/farmacologia
Disruptores Endócrinos/farmacologia
Fenóis/farmacologia
Raízes de Plantas/efeitos dos fármacos
Poluentes do Solo/farmacologia
Feijão de Soja/efeitos dos fármacos
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Hexoquinase/metabolismo
Isocitrato Desidrogenase/metabolismo
Magnésio/metabolismo
Fosfofrutoquinase-1/metabolismo
Fósforo/metabolismo
Raízes de Plantas/crescimento & desenvolvimento
Raízes de Plantas/metabolismo
Potássio/metabolismo
Piruvato Quinase/metabolismo
Plântulas/efeitos dos fármacos
Plântulas/crescimento & desenvolvimento
Plântulas/metabolismo
Feijão de Soja/crescimento & desenvolvimento
Feijão de Soja/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzhydryl Compounds); 0 (Endocrine Disruptors); 0 (Phenols); 0 (Soil Pollutants); 27YLU75U4W (Phosphorus); EC 1.1.1.41 (Isocitrate Dehydrogenase); EC 2.7.1.1 (Hexokinase); EC 2.7.1.11 (Phosphofructokinase-1); EC 2.7.1.40 (Pyruvate Kinase); I38ZP9992A (Magnesium); MLT3645I99 (bisphenol A); RWP5GA015D (Potassium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161011
[St] Status:MEDLINE


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[PMID]:27525435
[Au] Autor:Koppe L; Nyam E; Vivot K; Manning Fox JE; Dai XQ; Nguyen BN; Trudel D; Attané C; Moullé VS; MacDonald PE; Ghislain J; Poitout V
[Ti] Título:Urea impairs ß cell glycolysis and insulin secretion in chronic kidney disease.
[So] Source:J Clin Invest;126(9):3598-612, 2016 Sep 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic ß cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis.
[Mh] Termos MeSH primário: Glicólise
Células Secretoras de Insulina/metabolismo
Insulina/secreção
Falência Renal Crônica/metabolismo
Ureia/química
[Mh] Termos MeSH secundário: Animais
Antioxidantes/metabolismo
Cianatos/química
Modelos Animais de Doenças
Exocitose
Glucoquinase/metabolismo
Glucose/metabolismo
Teste de Tolerância a Glucose
Ilhotas Pancreáticas/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Estresse Oxidativo
Fosfofrutoquinase-1/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Uremia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Cyanates); 0 (Insulin); 0 (Reactive Oxygen Species); 8W8T17847W (Urea); EC 2.7.1.11 (Phosphofructokinase-1); EC 2.7.1.2 (Glucokinase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160816
[St] Status:MEDLINE


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[PMID]:27226568
[Au] Autor:Chan CY; Dominguez D; Parra KJ
[Ad] Endereço:From the Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
[Ti] Título:Regulation of Vacuolar H+-ATPase (V-ATPase) Reassembly by Glycolysis Flow in 6-Phosphofructo-1-kinase (PFK-1)-deficient Yeast Cells.
[So] Source:J Biol Chem;291(30):15820-9, 2016 07 22.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Yeast 6-phosphofructo-1-kinase (PFK-1) has two subunits, Pfk1p and Pfk2p. Deletion of Pfk2p alters glucose-dependent V-ATPase reassembly and vacuolar acidification (Chan, C. Y., and Parra, K. J. (2014) Yeast phosphofructokinase-1 subunit Pfk2p is necessary for pH homeostasis and glucose-dependent vacuolar ATPase reassembly. J. Biol. Chem. 289, 19448-19457). This study capitalized on the mechanisms suppressing vacuolar H(+)-ATPase (V-ATPase) in pfk2Δ to gain new knowledge of the mechanisms underlying glucose-dependent V-ATPase regulation. Because V-ATPase is fully assembled in pfk2Δ, and glycolysis partially suppressed at steady state, we manipulated glycolysis and assessed its direct involvement on V-ATPase function. At steady state, the ratio of proton transport to ATP hydrolysis increased 24% after increasing the glucose concentration from 2% to 4% to enhance the glycolysis flow in pfk2Δ. Tighter coupling restored vacuolar pH when glucose was abundant and glycolysis operated below capacity. After readdition of glucose to glucose-deprived cells, glucose-dependent V1Vo reassembly was proportional to the glycolysis flow. Readdition of 2% glucose to pfk2Δ cells, which restored 62% of ethanol concentration, led to equivalent 60% V1Vo reassembly levels. Steady-state level of assembly (100% reassembly) was reached at 4% glucose when glycolysis reached a threshold in pfk2Δ (≥40% the wild-type flow). At 4% glucose, the level of Pfk1p co-immunoprecipitated with V-ATPase decreased 58% in pfk2Δ, suggesting that Pfk1p binding to V-ATPase may be inhibitory in the mutant. We concluded that V-ATPase activity at steady state and V-ATPase reassembly after readdition of glucose to glucose-deprived cells are controlled by the glycolysis flow. We propose a new mechanism by which glucose regulates V-ATPase catalytic activity that occurs at steady state without changing V1Vo assembly.
[Mh] Termos MeSH primário: Glicólise
Fosfofrutoquinase-1/deficiência
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/enzimologia
ATPases Vacuolares Próton-Translocadoras/metabolismo
[Mh] Termos MeSH secundário: Etanol/metabolismo
Glucose/genética
Glucose/metabolismo
Concentração de Íons de Hidrogênio
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
ATPases Vacuolares Próton-Translocadoras/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Saccharomyces cerevisiae Proteins); 3K9958V90M (Ethanol); EC 2.7.1.11 (Phosphofructokinase-1); EC 3.6.1.- (Vacuolar Proton-Translocating ATPases); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160527
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.717488


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[PMID]:27153534
[Au] Autor:Li TY; Sun Y; Liang Y; Liu Q; Shi Y; Zhang CS; Zhang C; Song L; Zhang P; Zhang X; Li X; Chen T; Huang HY; He X; Wang Y; Wu YQ; Chen S; Jiang M; Chen C; Xie C; Yang JY; Lin Y; Zhao S; Ye Z; Lin SY; Chiu DT; Lin SC
[Ad] Endereço:State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, China.
[Ti] Título:ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy.
[So] Source:Mol Cell;62(3):359-370, 2016 May 05.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.
[Mh] Termos MeSH primário: Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo
Autofagia
Glucose/metabolismo
Glicólise
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Via de Pentose Fosfato
Proteínas Serina-Treonina Quinases/metabolismo
Estresse Fisiológico
[Mh] Termos MeSH secundário: Aminoácidos/deficiência
Aminoácidos/metabolismo
Animais
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/deficiência
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética
Biomarcadores Tumorais/metabolismo
Morte Celular
Proteínas de Ligação a DNA/metabolismo
Feminino
Frutose-Bifosfatase/metabolismo
Genótipo
Células HCT116
Hexoquinase/metabolismo
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Células MCF-7
Masculino
Camundongos Knockout
Fenótipo
Fosfofrutoquinase-1/metabolismo
Fosfopiruvato Hidratase/metabolismo
Fosforilação
Proteínas Serina-Treonina Quinases/deficiência
Proteínas Serina-Treonina Quinases/genética
Interferência de RNA
Espécies Reativas de Oxigênio/metabolismo
Transdução de Sinais
Fatores de Tempo
Transfecção
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Biomarkers, Tumor); 0 (DNA-Binding Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (Reactive Oxygen Species); 0 (Tumor Suppressor Proteins); EC 2.7.1.1 (HK1 protein, human); EC 2.7.1.1 (HK1 protein, mouse); EC 2.7.1.1 (Hexokinase); EC 2.7.1.11 (Phosphofructokinase-1); EC 2.7.1.11 (Ulk2 protein, mouse); EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (ULK1 protein, human); EC 2.7.11.1 (Ulk1 protein, mouse); EC 2.7.11.1 (Ulk2 protein, human); EC 3.1.3.11 (Fructose-Bisphosphatase); EC 4.2.1.11 (ENO1 protein, human); EC 4.2.1.11 (Eno1 protein, mouse); EC 4.2.1.11 (Phosphopyruvate Hydratase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE


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[PMID]:27150797
[Au] Autor:Yu TY; Morton JD; Clerens S; Dyer JM
[Ad] Endereço:Food & Bio-Based Products, AgResearch Lincoln Research Centre, Private Bag 4749, Christchurch 8140, New Zealand; Wine, Food & Molecular Biosciences, Lincoln University, Faculty of Agriculture and Life Sciences, PO Box 85084, Canterbury 7647, New Zealand. Electronic address: Robert.Yu@agresea
[Ti] Título:Proteomic investigation of protein profile changes and amino acid residue-level modification in cooked lamb longissimus thoracis et lumborum: The effect of roasting.
[So] Source:Meat Sci;119:80-8, 2016 Sep.
[Is] ISSN:1873-4138
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Protein modifications of meat cooked by typical dry-heat methods (e.g., roasting) are currently not well understood. The present study utilised a shotgun proteomic approach to examine the molecular-level effect of roasting on thin lamb longissimus thoracis et lumborum patties, in terms of changes to both the protein profile and amino acid residue side-chain modifications. Cooking caused aggregation of actin, myosin heavy chains and sarcoplasmic proteins. Longer roasting time resulted in significantly reduced protein extractability as well as protein truncation involving particularly a number of myofibrillar and sarcoplasmic proteins, e.g., 6-phosphofructokinase, beta-enolase, l-lactate dehydrogenase A chain, alpha-actinin-3, actin and possibly myosin heavy chains. Modifications that have potential influence on nutritional properties, including carboxyethyllysine and a potentially glucose-derived N-terminal Amadori compound, were observed in actin and myoglobin after roasting. This study provided new insights into molecular changes resulting from the dry-heat treatment of meat, such as commonly used in food preparation.
[Mh] Termos MeSH primário: Aminoácidos/análise
Culinária
Músculos Paraespinais/química
Proteômica
Carne Vermelha/análise
Retículo Sarcoplasmático/química
[Mh] Termos MeSH secundário: Actinina/química
Animais
Cromatografia Líquida
Temperatura Alta
L-Lactato Desidrogenase/química
Proteínas Musculares/química
Miofibrilas/química
Fosfofrutoquinase-1/química
Fosfopiruvato Hidratase/química
Ovinos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Muscle Proteins); 11003-00-2 (Actinin); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.7.1.11 (Phosphofructokinase-1); EC 4.2.1.11 (Phosphopyruvate Hydratase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170522
[Lr] Data última revisão:
170522
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160507
[St] Status:MEDLINE



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