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[PMID]:28455454
[Au] Autor:Onodera K; Sugiura H; Yamada M; Koarai A; Fujino N; Yanagisawa S; Tanaka R; Numakura T; Togo S; Sato K; Kyogoku Y; Hashimoto Y; Okazaki T; Tamada T; Kobayashi S; Yanai M; Miura M; Hoshikawa Y; Okada Y; Suzuki S; Ichinose M
[Ad] Endereço:Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
[Ti] Título:Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease.
[So] Source:Thorax;72(10):893-904, 2017 10.
[Is] ISSN:1468-3296
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor ß superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence. METHODS: The plasma levels of GDF11 were investigated in two separate cohorts by western blotting. The localisation and expression of GDF11 in the lungs were investigated by immunohistochemistry and quantitative reverse transcription PCR, respectively. The effects of GDF11 on both cigarette smoke extract (CSE)-induced cellular senescence in vitro and on elastase-induced cellular senescence in vivo were investigated. RESULTS: The levels of plasma GDF11 in the COPD group were decreased compared with the control groups in the two independent cohorts. The levels of plasma GDF11 were significantly positively correlated with pulmonary function data. The mRNA expression of GDF11 in mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE decreased the production of GDF11. Treatment with GDF11 significantly inhibited CSE-induced cellular senescence and upregulation of inflammatory mediators, partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated cellular senescence and airspace enlargement in an elastase-induced mouse model of emphysema. CONCLUSIONS: The decrease in GDF11 may be involved in the cellular senescence observed in COPD.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas/metabolismo
Senescência Celular
Fatores de Diferenciação de Crescimento/metabolismo
Doença Pulmonar Obstrutiva Crônica/metabolismo
[Mh] Termos MeSH secundário: Idoso
Animais
Western Blotting
Proteínas Morfogenéticas Ósseas/farmacologia
Modelos Animais de Doenças
Feminino
Fatores de Diferenciação de Crescimento/farmacologia
Seres Humanos
Imuno-Histoquímica
Masculino
Camundongos
Plasma
RNA Mensageiro/metabolismo
Testes de Função Respiratória
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fumaça/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (Gdf11 protein, mouse); 0 (Growth Differentiation Factors); 0 (RNA, Messenger); 0 (Smoke)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1136/thoraxjnl-2016-209352


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[PMID]:28450417
[Au] Autor:Li H; Li Y; Xiang L; Zhang J; Zhu B; Xiang L; Dong J; Liu M; Xiang G
[Ad] Endereço:Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
[Ti] Título:GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet ß-Cell Function and Survival.
[So] Source:Diabetes;66(7):1914-1927, 2017 07.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of ß-cells and improved glucose metabolism in both nongenetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused ß-cell failure and lethal T2D. In vitro treatment of isolated murine islets and MIN6 cells with recombinant GDF11 attenuated glucotoxicity-induced ß-cell dysfunction and apoptosis. Mechanistically, the GDF11-mediated protective effects could be attributed to the activation of transforming growth factor-ß/Smad2 and phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-FoxO1 signaling. These findings suggest that GDF11 repletion may improve ß-cell function and mass and thus may lead to a new therapeutic approach for T2D.
[Mh] Termos MeSH primário: Glicemia/efeitos dos fármacos
Proteínas Morfogenéticas Ósseas/farmacologia
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Fatores de Diferenciação de Crescimento/farmacologia
Células Secretoras de Insulina/efeitos dos fármacos
Insulina/secreção
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/farmacologia
Apoptose
Glicemia/metabolismo
Western Blotting
Proteínas Morfogenéticas Ósseas/antagonistas & inibidores
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Dieta Hiperlipídica
Modelos Animais de Doenças
Proteína Forkhead Box O1/efeitos dos fármacos
Proteína Forkhead Box O1/metabolismo
Teste de Tolerância a Glucose
Fatores de Diferenciação de Crescimento/antagonistas & inibidores
Células Secretoras de Insulina/secreção
Ilhotas Pancreáticas/efeitos dos fármacos
Ilhotas Pancreáticas/secreção
Camundongos
Fosfotransferases (Aceptor do Grupo Álcool)/efeitos dos fármacos
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Receptores para Leptina/genética
Transdução de Sinais/efeitos dos fármacos
Proteína Smad2/efeitos dos fármacos
Proteína Smad2/metabolismo
Fator de Crescimento Transformador beta/efeitos dos fármacos
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Blood Glucose); 0 (Bone Morphogenetic Proteins); 0 (Forkhead Box Protein O1); 0 (Foxo1 protein, mouse); 0 (Gdf11 protein, mouse); 0 (Growth Differentiation Factors); 0 (Insulin); 0 (Receptors, Leptin); 0 (Smad2 Protein); 0 (Smad2 protein, mouse); 0 (Transforming Growth Factor beta); 0 (leptin receptor, mouse); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.- (phosphatidylinositol 4,5-biphosphate kinase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.2337/db17-0086


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[PMID]:28715204
[Au] Autor:Pepinsky B; Gong BJ; Gao Y; Lehmann A; Ferrant J; Amatucci J; Sun Y; Bush M; Walz T; Pederson N; Cameron T; Wen D
[Ad] Endereço:Department of Biotherapeutics and Medicinal Sciences, Biogen , 115 Broadway, Cambridge, Massachusetts 02142, United States.
[Ti] Título:A Prodomain Fragment from the Proteolytic Activation of Growth Differentiation Factor 11 Remains Associated with the Mature Growth Factor and Keeps It Soluble.
[So] Source:Biochemistry;56(33):4405-4418, 2017 Aug 22.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 11 (GDF11), a member of the transforming growth factor ß (TGF-ß) family, plays diverse roles in mammalian development. It is synthesized as a large, inactive precursor protein containing a prodomain, pro-GDF11, and exists as a homodimer. Activation requires two proteolytic processing steps that release the prodomains and transform latent pro-GDF11 into active mature GDF11. In studying proteolytic activation in vitro, we discovered that a 6-kDa prodomain peptide containing residues 60-114, PDP , remained associated with the mature growth factor. Whereas the full-length prodomain of GDF11 is a functional antagonist, PDP had no impact on activity. The specific activity of the GDF11/PDP complex (EC = 1 nM) in a SMAD2/3 reporter assay was identical to that of mature GDF11 alone. PDP improved the solubility of mature GDF11 at neutral pH. As the growth factor normally aggregates/precipitates at neutral pH, PDP can be used as a solubility-enhancing formulation. Expression of two engineered constructs with PDP genetically fused to the mature domain of GDF11 through a 2x or 3x G4S linker produced soluble monomeric products that could be dimerized through redox reactions. The construct with a 3x G4S linker retained 10% activity (EC = 10 nM), whereas the construct connected with a 2x G4S linker could only be activated (EC = 2 nM) by protease treatment. Complex formation with PDP represents a new strategy for stabilizing GDF11 in an active state that may translate to other members of the TGF-ß family that form latent pro/mature domain complexes.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas
Fatores de Diferenciação de Crescimento
Multimerização Proteica
Proteólise
[Mh] Termos MeSH secundário: Animais
Proteínas Morfogenéticas Ósseas/biossíntese
Proteínas Morfogenéticas Ósseas/química
Proteínas Morfogenéticas Ósseas/genética
Células CHO
Cricetinae
Cricetulus
Fatores de Diferenciação de Crescimento/biossíntese
Fatores de Diferenciação de Crescimento/química
Fatores de Diferenciação de Crescimento/genética
Seres Humanos
Concentração de Íons de Hidrogênio
Peptídeos/química
Peptídeos/genética
Peptídeos/metabolismo
Domínios Proteicos
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (GDF11 protein, human); 0 (Growth Differentiation Factors); 0 (Peptides)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00302


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[PMID]:28646109
[Au] Autor:Mitrofan CG; Appleby SL; Nash GB; Mallat Z; Chilvers ER; Upton PD; Morrell NW
[Ad] Endereço:From the Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ and.
[Ti] Título:Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2.
[So] Source:J Biol Chem;292(33):13714-13726, 2017 Aug 18.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Using siRNAs to type I and II BMP receptors and the signaling intermediaries (Smads), we demonstrated a key role for ALK2 in the BMP9/BMP10-induced surface expression of E-selectin, and both ALK1 and ALK2 in the up-regulation of VCAM-1 and ICAM-1. The type II receptors, BMPR-II and ACTR-IIA were both required for this response, as was Smad1/5. The up-regulation of cell surface adhesion molecules by BMP9/10 in the presence of TNFα was inhibited by LDN193189, which inhibits ALK2 but not ALK1. Furthermore, LDN193189 inhibited monocyte recruitment induced by TNFα and BMP9/10. BMP9/10 increased basal IκBα protein expression, but did not alter p65/RelA levels. Our findings suggest that higher concentrations of BMP9/BMP10 synergize with TNFα to induce the up-regulation of endothelial selectins and adhesion molecules, ultimately resulting in increased monocyte recruitment to the vascular endothelium. This process is mediated mainly via the ALK2 type I receptor, BMPR-II/ACTR-IIA type II receptors, and downstream Smad1/5 signaling.
[Mh] Termos MeSH primário: Receptores de Ativinas Tipo I/metabolismo
Proteínas Morfogenéticas Ósseas/metabolismo
Endotélio Vascular/metabolismo
Fatores de Diferenciação de Crescimento/metabolismo
Monócitos/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Receptores de Ativinas Tipo I/antagonistas & inibidores
Receptores de Ativinas Tipo I/genética
Receptores de Activinas Tipo II/antagonistas & inibidores
Receptores de Activinas Tipo II/genética
Receptores de Activinas Tipo II/metabolismo
Aorta
Adesão Celular/efeitos dos fármacos
Células Cultivadas
Selectina E/química
Selectina E/genética
Selectina E/metabolismo
Endotélio Vascular/citologia
Endotélio Vascular/efeitos dos fármacos
Endotélio Vascular/imunologia
Seres Humanos
Molécula 1 de Adesão Intercelular/química
Molécula 1 de Adesão Intercelular/genética
Molécula 1 de Adesão Intercelular/metabolismo
Cinética
Monócitos/citologia
Monócitos/efeitos dos fármacos
Monócitos/imunologia
Fosforilação/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Processamento de Proteína Pós-Traducional/efeitos dos fármacos
Pirazóis/farmacologia
Pirimidinas/farmacologia
Interferência de RNA
Transdução de Sinais/efeitos dos fármacos
Fator de Necrose Tumoral alfa/agonistas
Regulação para Cima/efeitos dos fármacos
Molécula 1 de Adesão de Célula Vascular/química
Molécula 1 de Adesão de Célula Vascular/genética
Molécula 1 de Adesão de Célula Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BMP10 protein, human); 0 (Bone Morphogenetic Proteins); 0 (E-Selectin); 0 (GDF2 protein, human); 0 (Growth Differentiation Factors); 0 (ICAM1 protein, human); 0 (LDN 193189); 0 (Protein Kinase Inhibitors); 0 (Pyrazoles); 0 (Pyrimidines); 0 (SELE protein, human); 0 (TNF protein, human); 0 (Tumor Necrosis Factor-alpha); 0 (Vascular Cell Adhesion Molecule-1); 126547-89-5 (Intercellular Adhesion Molecule-1); EC 2.7.11.30 (ACVR1 protein, human); EC 2.7.11.30 (ACVRL1 protein, human); EC 2.7.11.30 (Activin Receptors, Type I); EC 2.7.11.30 (Activin Receptors, Type II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.778506


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[PMID]:28611236
[Au] Autor:Yang R; Fu S; Zhao L; Zhen B; Ye L; Niu X; Li X; Zhang P; Bai J
[Ad] Endereço:Department of Orthopedics, First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100048, China.
[Ti] Título:Quantitation of circulating GDF-11 and ß2-MG in aged patients with age-related impairment in cognitive function.
[So] Source:Clin Sci (Lond);131(15):1895-1904, 2017 Aug 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Growth differentiation factor 11 (GDF-11) has been implicated in reverse effects of ageing on the central nervous system of humans. ß2-microglobulin (ß2-MG) has been reported to negatively regulate cognition. However, there is a lot of controversy about the role of GDF-11 and ß2-MG in ageing and cognitive regulation. To examine the involvement of GDF-11 and ß2-MG in the ageing process and cognitive dysfunction, a total of 51 healthy subjects and 41 elderly patients with different degrees of age-related cognitive impairment participated in the study. We measured plasma GDF-11 and ß2-MG levels using ELISA and immunoturbidimetry, respectively. The results were statistically analyzed to evaluate the associations between levels of GDF-11 and ß2-MG, and ageing and cognitive impairments. Circulating GDF-11 levels did not decline with age or correlate with ageing in healthy Chinese males. We did not detect differences in circulating GDF-11 levels amongst the healthy advanced age and four cognitive impairment groups. ß2-MG levels increased with age, but there was no significant difference between healthy elderly males and advanced age males. Increased levels of ß2-MG were observed in the dementia group compared with the healthy advanced age group. Our results suggest that circulating GDF-11 may not exert a protective effect during the ageing process or on cognitive function, and ß2-MG may play a role in ageing and cognitive impairment. However, it is possible that the relatively small sample size in the present study affected the quality of the statistical analysis, and future studies are needed to further validate our findings.
[Mh] Termos MeSH primário: Envelhecimento/sangue
Proteínas Morfogenéticas Ósseas/sangue
Transtornos Cognitivos/sangue
Fatores de Diferenciação de Crescimento/sangue
Microglobulina-2 beta/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/sangue
Biomarcadores/sangue
Proteína C-Reativa/metabolismo
Demência Vascular/sangue
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Bone Morphogenetic Proteins); 0 (GDF11 protein, human); 0 (Growth Differentiation Factors); 0 (beta 2-Microglobulin); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.1042/CS20171028


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[PMID]:28533206
[Au] Autor:Augustin H; McGourty K; Steinert JR; Cochemé HM; Adcott J; Cabecinha M; Vincent A; Halff EF; Kittler JT; Boucrot E; Partridge L
[Ad] Endereço:Institute of Healthy Ageing, and GEE, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
[Ti] Título:Myostatin-like proteins regulate synaptic function and neuronal morphology.
[So] Source:Development;144(13):2445-2455, 2017 07 01.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Growth factors of the TGFß superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth.
[Mh] Termos MeSH primário: Forma Celular
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/metabolismo
Miostatina/metabolismo
Neurônios/citologia
Neurônios/metabolismo
Sinapses/metabolismo
Fator de Crescimento Transformador beta/metabolismo
[Mh] Termos MeSH secundário: Animais
Peso Corporal
Regulação para Baixo/genética
Drosophila melanogaster/citologia
Inativação Gênica
Quinase 3 da Glicogênio Sintase/metabolismo
Fatores de Diferenciação de Crescimento/metabolismo
Seres Humanos
Larva/metabolismo
Células Musculares/metabolismo
Neuroglia/metabolismo
Junção Neuromuscular/metabolismo
Ratos
Transdução de Sinais
Transmissão Sináptica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Gdf11 protein, rat); 0 (Growth Differentiation Factors); 0 (MSTN protein, human); 0 (Myostatin); 0 (Transforming Growth Factor beta); 0 (myoglianin protein, Drosophila); EC 2.7.11.1 (shaggy protein, Drosophila); EC 2.7.11.26 (Glycogen Synthase Kinase 3)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE
[do] DOI:10.1242/dev.152975


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[PMID]:28485800
[Au] Autor:Jing YY; Li D; Wu F; Gong LL; Li R
[Ad] Endereço:Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. rongli232006@163.com.
[Ti] Título:GDF11 does not improve the palmitate induced insulin resistance in C2C12.
[So] Source:Eur Rev Med Pharmacol Sci;21(8):1795-1802, 2017 Apr.
[Is] ISSN:2284-0729
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro. The mRNA expression of GDF11, GLUT4, IRS-1 (insulin receptor substrate-1) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GDF11 and PGC-1α were detected by Western blot. The glucose uptake was measured by 2NBDG uptake assay. RESULTS: In high fat diet induced obese mice, both serum level of GDF11 and the expression of GDF11 in skeletal muscle decreased. Similarly, the expression of GDF11 also reduced in palmitate-treated C2C12 myotubes. In vitro, the glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α significantly decreased after palmitate intervention, but GDF11 treatment did not reverse the reduction of glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α in C2C12 myotubes. CONCLUSIONS: We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate-treated myotubes, but supplementation GDF11 does not ameliorate the palmitate-induced insulin resistance in C2C12 myotubes.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas/metabolismo
Fatores de Diferenciação de Crescimento/metabolismo
Resistência à Insulina
Fibras Musculares Esqueléticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Dieta Hiperlipídica
Transportador de Glucose Tipo 4/metabolismo
Insulina/metabolismo
Proteínas Substratos do Receptor de Insulina/metabolismo
Camundongos
Fibras Musculares Esqueléticas/efeitos dos fármacos
Músculo Esquelético/efeitos dos fármacos
Músculo Esquelético/metabolismo
Obesidade/metabolismo
Palmitatos
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (Gdf11 protein, mouse); 0 (Glucose Transporter Type 4); 0 (Growth Differentiation Factors); 0 (Insulin); 0 (Insulin Receptor Substrate Proteins); 0 (Irs1 protein, mouse); 0 (Palmitates); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 0 (Ppargc1a protein, mouse); 0 (Slc2a4 protein, mouse)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


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[PMID]:28478937
[Au] Autor:Qin X; Kuang H; Chen L; Wei S; Yu D; Liang F
[Ad] Endereço:Graduate School, Guangxi Medical University, Nanning, Guangxi, China.
[Ti] Título:Coexpression of growth differentiation factor 11 and reactive oxygen species in metastatic oral cancer and its role in inducing the epithelial to mesenchymal transition.
[So] Source:Oral Surg Oral Med Oral Pathol Oral Radiol;123(6):697-706, 2017 Jun.
[Is] ISSN:2212-4411
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim of this study was to investigate growth differentiation factor 11 (GDF11) and reactive oxygen species (ROS) expression in metastatic oral cancer and explored their roles in inducing epithelial to mesenchymal transition (EMT). STUDY DESIGN: The expression of GDF11, ROS, and EMT-related markers was evaluated in primary tumor tissues from patients with oral squamous cell carcinoma (OSCC). SCC-9 cells, a human tongue carcinoma cell line, were treated with recombinant GDF11. Induction of EMT, expression of EMT-related markers, and the effect of ROS on EMT in SCC-9 cells were analyzed. RESULTS: Overexpression of GDF11 and ROS was observed in patients with metastatic oral cancer. Downregulated expression of E-cadherin and upregulated expression of vimentin, δ-EF1, SIP-1, MMP-2, and MMP-9 were observed in patients with metastatic oral cancer, relative to the expression of these factors in patients with nonmetastatic oral cancer. With recombinant GDF11 treatment, obvious spindle-shaped cells appeared, and gene expressions of EMT-related markers were altered in SCC-9 cells. Treatment with the powerful antioxidant N-acetylcysteine inhibited GDF11-induced EMT and cell migration. CONCLUSIONS: GDF11 induces EMT and cell migration with ROS involvement in SCC-9 cells. Overexpression of GDF11 and ROS is associated with metastatic oral cancer. GDF11 and ROS may participate in metastasis of oral cancer through EMT.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas/metabolismo
Carcinoma de Células Escamosas/metabolismo
Transição Epitelial-Mesenquimal
Fatores de Diferenciação de Crescimento/metabolismo
Neoplasias Bucais/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/metabolismo
Carcinoma de Células Escamosas/patologia
Movimento Celular
Seres Humanos
Imuno-Histoquímica
Neoplasias Bucais/patologia
Metástase Neoplásica
Reação em Cadeia da Polimerase
Estudos Prospectivos
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Bone Morphogenetic Proteins); 0 (GDF11 protein, human); 0 (Growth Differentiation Factors); 0 (Reactive Oxygen Species)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE


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[PMID]:28270449
[Au] Autor:Hammers DW; Merscham-Banda M; Hsiao JY; Engst S; Hartman JJ; Sweeney HL
[Ad] Endereço:Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA.
[Ti] Título:Supraphysiological levels of GDF11 induce striated muscle atrophy.
[So] Source:EMBO Mol Med;9(4):531-544, 2017 Apr.
[Is] ISSN:1757-4684
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor ß superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the effects of GDF11 on skeletal muscle mass have not been addressed. Using myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities/potencies on activating p-SMAD2/3 and induce comparable levels of differentiated myotube atrophy. We further demonstrate that adeno-associated virus-mediated systemic overexpression of GDF11 in C57BL/6 mice results in substantial atrophy of skeletal and cardiac muscle, inducing a cachexic phenotype not seen in mice expressing similar levels of Mstn. Greater cardiac expression of may explain this GDF11-specific cardiac phenotype. These data indicate that bioactive GDF11 at supraphysiological levels cause wasting of both skeletal and cardiac muscle. Rather than a therapeutic agent, GDF11 should be viewed as a potential deleterious biomarker in muscle wasting diseases.
[Mh] Termos MeSH primário: Atrofia
Proteínas Morfogenéticas Ósseas/biossíntese
Fatores de Diferenciação de Crescimento/biossíntese
Músculo Estriado/patologia
[Mh] Termos MeSH secundário: Animais
Dependovirus/genética
Expressão Gênica
Camundongos Endogâmicos C57BL
Fibras Musculares Esqueléticas/metabolismo
Mioblastos/efeitos dos fármacos
Miostatina
Proteína Smad2/metabolismo
Proteína Smad3/metabolismo
Transdução Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (Gdf11 protein, mouse); 0 (Growth Differentiation Factors); 0 (Mstn protein, mouse); 0 (Myostatin); 0 (Smad2 Protein); 0 (Smad3 Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.15252/emmm.201607231


  10 / 307 MEDLINE  
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[PMID]:28257634
[Au] Autor:Walker RG; Czepnik M; Goebel EJ; McCoy JC; Vujic A; Cho M; Oh J; Aykul S; Walton KL; Schang G; Bernard DJ; Hinck AP; Harrison CA; Martinez-Hackert E; Wagers AJ; Lee RT; Thompson TB
[Ad] Endereço:Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH, 45267, USA.
[Ti] Título:Structural basis for potency differences between GDF8 and GDF11.
[So] Source:BMC Biol;15(1):19, 2017 Mar 03.
[Is] ISSN:1741-7007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor ß (TGFß) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Resolution of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 crystal structures reveals unique properties of both ligands, specifically in the type I receptor binding site. Lastly, substitution of GDF11 residues into GDF8 confers enhanced activity to GDF8. CONCLUSIONS: These studies identify distinctive structural features of GDF11 that enhance its potency, relative to GDF8; however, the biological consequences of these differences remain to be determined.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas/química
Fatores de Diferenciação de Crescimento/química
Miostatina/química
Miostatina/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Proteínas Morfogenéticas Ósseas/antagonistas & inibidores
Proteínas Morfogenéticas Ósseas/metabolismo
Células Cultivadas
Cristalografia por Raios X
Folistatina/metabolismo
Genes Reporter
Fatores de Diferenciação de Crescimento/antagonistas & inibidores
Fatores de Diferenciação de Crescimento/metabolismo
Seres Humanos
Injeções Intravenosas
Ligantes
Luciferases/metabolismo
Camundongos
Modelos Moleculares
Mioblastos/metabolismo
Miocárdio/metabolismo
Miostatina/antagonistas & inibidores
Fosforilação
Ligação Proteica
Proteínas Serina-Treonina Quinases/metabolismo
Receptores de Fatores de Crescimento Transformadores beta/metabolismo
Alinhamento de Sequência
Transdução de Sinais
Proteínas Smad/metabolismo
Homologia Estrutural de Proteína
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (Follistatin); 0 (GDF11 protein, human); 0 (Growth Differentiation Factors); 0 (Ligands); 0 (Myostatin); 0 (Receptors, Transforming Growth Factor beta); 0 (Smad Proteins); EC 1.13.12.- (Luciferases); EC 2.7.1.11 (TGF-beta type I receptor); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE
[do] DOI:10.1186/s12915-017-0350-1



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