Base de dados : MEDLINE
Pesquisa : D08.811.277.040.330.300.200.100.400 [Categoria DeCS]
Referências encontradas : 1883 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 189 ir para página                         

  1 / 1883 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28453643
[Au] Autor:Grüters-Kieslich A; Reyes M; Sharma A; Demirci C; DeClue TJ; Lankes E; Tiosano D; Schnabel D; Jüppner H
[Ad] Endereço:Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
[Ti] Título:Early-Onset Obesity: Unrecognized First Evidence for GNAS Mutations and Methylation Changes.
[So] Source:J Clin Endocrinol Metab;102(8):2670-2677, 2017 Aug 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Early-onset obesity, characteristic for disorders affecting the leptin-melanocortin pathway, is also observed in pseudohypoparathyroidism type 1A (PHP1A), a disorder caused by maternal GNAS mutations that disrupt expression or function of the stimulatory G protein α-subunit (Gsα). Mutations and/or epigenetic abnormalities at the same genetic locus are also the cause of pseudohypoparathyroidism type 1B (PHP1B). However, although equivalent biochemical and radiographic findings can be encountered in these related disorders caused by GNAS abnormalities, they are considered distinct clinical entities. Objectives: To further emphasize the overlapping features between both disorders, we report the cases of several children, initially brought to medical attention because of unexplained early-onset obesity, in whom PHP1B or PHP1A was eventually diagnosed. Patients and Methods: Search for GNAS methylation changes or mutations in cohorts of patients with early-onset obesity. Results: Severe obesity had been noted in five infants, with a later diagnosis of PHP1B due to STX16 deletions and/or abnormal GNAS methylation. These findings prompted analysis of 24 unselected obese patients, leading to the discovery of inherited STX16 deletions in 2 individuals. Similarly, impressive early weight gains were noted in five patients, who initially lacked additional Albright hereditary osteodystrophy features but in whom PHP1A due to GNAS mutations involving exons encoding Gsα was diagnosed. Conclusions: Obesity during the first year of life can be the first clinical evidence for PHP1B, expanding the spectrum of phenotypic overlap between PHP1A and PHP1B. Importantly, GNAS methylation abnormalities escape detection by targeted or genome-wide sequencing strategies, raising the question of whether epigenetic GNAS analyses should be considered for unexplained obesity.
[Mh] Termos MeSH primário: Cromograninas/genética
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética
Obesidade Pediátrica/genética
Pseudo-Hipoparatireoidismo/genética
Sintaxina 16/genética
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Estudos de Coortes
Metilação de DNA
Epigênese Genética
Feminino
Seres Humanos
Lactente
Masculino
Reação em Cadeia da Polimerase Multiplex
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromogranins); 0 (STX16 protein, human); 0 (Syntaxin 16); EC 3.6.1.- (GNAS protein, human); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00395


  2 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29402888
[Au] Autor:Yano H; Cai NS; Xu M; Verma RK; Rea W; Hoffman AF; Shi L; Javitch JA; Bonci A; Ferré S
[Ad] Endereço:National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. hideaki.yano@nih.gov.
[Ti] Título:Gs- versus Golf-dependent functional selectivity mediated by the dopamine D receptor.
[So] Source:Nat Commun;9(1):486, 2018 02 05.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant in the striatum, while Gs is predominant in the cortex. Yet, little is known about their functional distinctions. The dopamine D receptor (D1R) couples to Gs/olf and is highly expressed in cortical and striatal areas, making it an important therapeutic target for neuropsychiatric disorders. Using novel drug screening methods that allow analysis of specific G-protein subtype coupling, we found that, relative to dopamine, dihydrexidine and N-propyl-apomorphine behave as full D1R agonists when coupled to Gs, but as partial D1R agonists when coupled to Golf. The Gs/Golf-dependent biased agonism by dihydrexidine was consistently observed at the levels of cellular signaling, neuronal function, and behavior. Our findings of Gs/Golf-dependent functional selectivity in D1R ligands open a new avenue for the treatment of cortex-specific or striatum-specific neuropsychiatric dysfunction.
[Mh] Termos MeSH primário: Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo
Fenantridinas/farmacologia
Receptores de Dopamina D1/agonistas
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação
Encéfalo/metabolismo
Linhagem Celular Tumoral
Subunidades alfa de Proteínas de Ligação ao GTP/genética
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Camundongos
Conformação Proteica
Receptores de Dopamina D1/genética
Receptores de Dopamina D1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GTP-Binding Protein alpha Subunits); 0 (Phenanthridines); 0 (Receptors, Dopamine D1); 0 (olfactory G protein subunit alpha olf); 32D64VH037 (dihydrexidine); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02606-w


  3 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28741526
[Au] Autor:Innamorati G; Valenti MT; Giacomello L; Dalle Carbonare L; Bassi C
[Ad] Endereço:Laboratory of Translational Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics. University of Verona, Verona, Italy. Electronic address: giulio.innamorati@univr.it.
[Ti] Título:GNAS Mutations: Drivers or Co-Pilots? Yet, Promising Diagnostic Biomarkers.
[So] Source:Trends Cancer;2(6):282-285, 2016 Jun.
[Is] ISSN:2405-8025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Over 25 years ago, GNAS mutations were discovered associated with McCune-Albright syndrome (MAS) and pituitary tumors. The mutant gene, encoding the heterotrimeric Gs protein, was named 'derived from Gs Protein' (gsp) oncogene. For a long time, gsp remained associated with specific endocrine tumors. Recently, high frequencies of gsp were reported for a rapidly growing number of neoplasms in the gastrointestinal tract. Will heterotrimeric G-proteins follow small G-proteins and become recognized as cancer biomarkers and therapeutic targets?
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Cromograninas/genética
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética
Neoplasias/genética
[Mh] Termos MeSH secundário: Seres Humanos
Mutação
Neoplasias/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranins); EC 3.6.1.- (GNAS protein, human); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  4 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29054409
[Au] Autor:Nakashima N; Nakashima K; Nakayama T; Takaku A; Kanamori R
[Ad] Endereço:Division of Integrated Autonomic Function, Department of Physiology, School of Medicine, Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Department of Physiology and Neurobiology, Faculty of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan. Electronic ad
[Ti] Título:Dual expression of constitutively active Gα -protein-coupled receptors differentially establishes the resting activity of the cAMP-gated HCN2 channel in a single compartment.
[So] Source:Biochem Biophys Res Commun;494(1-2):76-81, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channel is a major subtype of the HCN channel family expressed in the nervous system that sets the membrane potential, regulates cell excitability and senses changes in the extracellular environment. Neurons express various Gα -protein-coupled receptors (GPCRs), many of which show ligand-independent constitutive activity. These membrane-bound proteins are expressed in various subcellular compartments of neurons. Therefore, some proportion of HCN2 channels opens in response to the basal cAMP pool size produced by constitutively active GPCRs. Here, we employed an exogenous HEK293 expression system and voltage-clamp patch-clamp recordings to investigate basal HCN2 channel activity in the presence of two GPCRs with diverse basal activities in a single compartment. We utilized the ß2-adrenoceptor (ß2AR) together with odorant receptors (ORs), as both GPCR families are known to show strong basal activity. Consequently, ß2AR alone strongly enhanced the activity of HCN2 channels, and co-expression of ORs further diversified the HCN2 channel activity, which was totally abolished by an adenylate cyclase inhibitor. Thus, we conclude that the dual expression of constitutively active GPCRs establishes the diverse range of the basal cAMP pool size in resting cells through mutual additive or suppressive interactions, even in the absence of external stimulation.
[Mh] Termos MeSH primário: AMP Cíclico/metabolismo
Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo
Canais de Potássio/metabolismo
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética
Ativação do Canal Iônico
Técnicas de Patch-Clamp
Canais de Potássio/genética
Receptores Adrenérgicos beta 2/genética
Receptores Adrenérgicos beta 2/metabolismo
Receptores Acoplados a Proteínas-G/genética
Receptores Odorantes/genética
Receptores Odorantes/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HCN2 protein, human); 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels); 0 (Potassium Channels); 0 (Receptors, Adrenergic, beta-2); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Odorant); 0 (Recombinant Proteins); E0399OZS9N (Cyclic AMP); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171022
[St] Status:MEDLINE


  5 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28834809
[Au] Autor:Hodgson A; Amemiya Y; Seth A; Djordjevic B; Parra-Herran C
[Ad] Endereço:Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
[Ti] Título:High-grade Müllerian Adenosarcoma: Genomic and Clinicopathologic Characterization of a Distinct Neoplasm With Prevalent TP53 Pathway Alterations and Aggressive Behavior.
[So] Source:Am J Surg Pathol;41(11):1513-1522, 2017 Nov.
[Is] ISSN:1532-0979
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Müllerian adenosarcoma harbors low malignant potential, except in cases with myometrial invasion or sarcomatous overgrowth. The presence of a high-grade stromal component has been proposed as an important pathologic predictor of outcome. We hypothesized that high-grade adenosarcoma has distinct clinical and molecular features, distinct from low-grade adenosarcoma. We analyzed the clinicopathologic features and follow-up of 9 high-grade adenosarcomas and a control group of 9 low-grade adenosarcomas. Comprehensive genomic analysis of the high-grade group was performed targeting exons of 409 oncogenes and tumor suppressor genes. In 1 case, the high-grade and low-grade components were separately sequenced. High-grade and low-grade adenosarcomas were comparable in patient age, myometrial invasion, and stage at presentation. Sarcomatous overgrowth was observed in 2/9 (22%) low-grade and 8/9 (89%) high-grade adenosarcomas. Six of 9 (67%) patients with high-grade adenosarcoma developed rapid recurrence; 1 died of her disease. Conversely, no low-grade tumors recurred or metastasized. Sequencing of high-grade adenosarcomas revealed frequent TP53 pathway alterations, identified in 7/9 (78%) cases. p53 expression by immunohistochemistry highly correlated with mutation status. Copy number variations occurred at a mean of 28.8 per tumor; most frequently involved genes included CDK4, MDM2, GNAS, SGK1, and DICER1. High-grade adenosarcoma is an aggressive neoplasm with propensity for short-interval recurrence and metastasis. The proportion of copy number alterations is similar to that reported for adenosarcoma with sarcomatous overgrowth. However, the high frequency of TP53 abnormalities is a novel finding, indicating that high-grade adenosarcoma is a distinct subset with driver TP53 pathway alterations. p53 immunohistochemistry can be used to confirm the presence of a high-grade component. Given its aggressive potential, the presence of any high-grade component in an adenosarcoma should be reported, even in the absence of sarcomatous overgrowth.
[Mh] Termos MeSH primário: Adenossarcoma/genética
Adenossarcoma/secundário
Biomarcadores Tumorais/genética
Mutação
Proteína Supressora de Tumor p53/genética
Neoplasias Uterinas/genética
Neoplasias Uterinas/patologia
[Mh] Termos MeSH secundário: Adenossarcoma/mortalidade
Adenossarcoma/terapia
Adulto
Idoso
Biomarcadores Tumorais/análise
Biópsia
Estudos de Casos e Controles
Cromograninas
Quinase 4 Dependente de Ciclina
RNA Helicases DEAD-box
Variações do Número de Cópias de DNA
Análise Mutacional de DNA
Progressão da Doença
Feminino
Subunidades alfa Gs de Proteínas de Ligação ao GTP
Dosagem de Genes
Perfilação da Expressão Gênica
Predisposição Genética para Doença
Seres Humanos
Proteínas Imediatamente Precoces
Imuno-Histoquímica
Meia-Idade
Gradação de Tumores
Recidiva Local de Neoplasia
Fenótipo
Proteínas Serina-Treonina Quinases
Proteínas Proto-Oncogênicas c-mdm2
Ribonuclease III
Fatores de Tempo
Resultado do Tratamento
Proteína Supressora de Tumor p53/análise
Neoplasias Uterinas/mortalidade
Neoplasias Uterinas/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranins); 0 (Immediate-Early Proteins); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); EC 2.3.2.27 (MDM2 protein, human); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (serum-glucocorticoid regulated kinase); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4); EC 3.1.26.3 (DICER1 protein, human); EC 3.1.26.3 (Ribonuclease III); EC 3.6.1.- (Gnas protein, mouse); EC 3.6.4.13 (DEAD-box RNA Helicases); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1097/PAS.0000000000000907


  6 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28715443
[Au] Autor:Chiang IN; Pu YS; Huang CY; Young TH
[Ad] Endereço:Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
[Ti] Título:Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.
[So] Source:PLoS One;12(7):e0180872, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Apoptose/efeitos da radiação
Cisplatino/toxicidade
Raios Infravermelhos
Túbulos Renais Proximais/efeitos da radiação
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/efeitos da radiação
Células Cultivadas
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética
Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Transportador de Glucose Tipo 1/genética
Transportador de Glucose Tipo 1/metabolismo
Seres Humanos
Túbulos Renais Proximais/citologia
Túbulos Renais Proximais/efeitos dos fármacos
Túbulos Renais Proximais/metabolismo
Masculino
Microscopia de Fluorescência
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Coelhos
Reação em Cadeia da Polimerase em Tempo Real
Receptores do Fator Natriurético Atrial/genética
Receptores do Fator Natriurético Atrial/metabolismo
ATPase Trocadora de Sódio-Potássio/genética
ATPase Trocadora de Sódio-Potássio/metabolismo
Regulação para Cima/efeitos dos fármacos
Regulação para Cima/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucose Transporter Type 1); 0 (Nerve Tissue Proteins); 0 (neuronal Cdk5 activator (p25-p35)); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs); EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180872


  7 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28705698
[Au] Autor:Woolley MJ; Reynolds CA; Simms J; Walker CS; Mobarec JC; Garelja ML; Conner AC; Poyner DR; Hay DL
[Ad] Endereço:Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
[Ti] Título:Receptor activity-modifying protein dependent and independent activation mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin receptors to Gs.
[So] Source:Biochem Pharmacol;142:96-110, 2017 Oct 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, and one of three receptor activity-modifying proteins (RAMPs). How CGRP and AM activate CLR and how this process is modulated by RAMPs is unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP heteromers by measuring the effect of targeted mutagenesis in the CLR transmembrane domain on cAMP production, modeling the active state conformations of CGRP and AM receptors in complex with the Gs C-terminus and conducting molecular dynamics simulations in an explicitly hydrated lipidic bilayer. The largest effects on receptor signaling were seen with H295A , I298A , L302A , N305A , L345A and E348A , F349A and H374A (class B numbering in superscript). Many of these residues are likely to form part of a group in close proximity to the peptide binding site and link to a network of hydrophilic and hydrophobic residues, which undergo rearrangements to facilitate Gs binding. Residues closer to the extracellular loops displayed more pronounced RAMP or ligand-dependent effects. Mutation of H374 to alanine increased AM potency 100-fold in the CGRP receptor. The molecular dynamics simulation showed that TM5 and TM6 pivoted around TM3. The data suggest that hydrophobic interactions are more important for CLR activation than other class B GPCRs, providing new insights into the mechanisms of activation of this class of receptor. Furthermore the data may aid in the understanding of how RAMPs modulate the signaling of other class B GPCRs.
[Mh] Termos MeSH primário: Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Proteína Semelhante a Receptor de Calcitonina/metabolismo
Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Proteínas Modificadoras da Atividade de Receptores/metabolismo
Receptores de Adrenomedulina/metabolismo
[Mh] Termos MeSH secundário: Animais
Células COS
Peptídeo Relacionado com Gene de Calcitonina/química
Peptídeo Relacionado com Gene de Calcitonina/genética
Proteína Semelhante a Receptor de Calcitonina/química
Proteína Semelhante a Receptor de Calcitonina/genética
Cercopithecus aethiops
AMP Cíclico/metabolismo
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Simulação de Dinâmica Molecular
Mutação
Ligação Proteica
Ensaio Radioligante
Proteínas Modificadoras da Atividade de Receptores/química
Proteínas Modificadoras da Atividade de Receptores/genética
Receptores de Adrenomedulina/química
Receptores de Adrenomedulina/genética
Proteínas Recombinantes de Fusão
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcitonin Receptor-Like Protein); 0 (Receptor Activity-Modifying Proteins); 0 (Receptors, Adrenomedullin); 0 (Recombinant Fusion Proteins); 83652-28-2 (Calcitonin Gene-Related Peptide); E0399OZS9N (Cyclic AMP); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE


  8 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28607487
[Au] Autor:Gregorio GG; Masureel M; Hilger D; Terry DS; Juette M; Zhao H; Zhou Z; Perez-Aguilar JM; Hauge M; Mathiasen S; Javitch JA; Weinstein H; Kobilka BK; Blanchard SC
[Ad] Endereço:Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
[Ti] Título:Single-molecule analysis of ligand efficacy in ß AR-G-protein activation.
[So] Source:Nature;547(7661):68-73, 2017 07 06.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:G-protein-coupled receptor (GPCR)-mediated signal transduction is central to human physiology and disease intervention, yet the molecular mechanisms responsible for ligand-dependent signalling responses remain poorly understood. In class A GPCRs, receptor activation and G-protein coupling entail outward movements of transmembrane helix 6 (TM6). Here, using single-molecule fluorescence resonance energy transfer imaging, we examine TM6 movements in the ß adrenergic receptor (ß AR) upon exposure to orthosteric ligands with different efficacies, in the absence and presence of the G heterotrimer. We show that partial and full agonists differentially affect TM6 motions to regulate the rate at which GDP-bound ß AR-G complexes are formed and the efficiency of nucleotide exchange leading to G activation. These data also reveal transient nucleotide-bound ß AR-G species that are distinct from known structures, and provide single-molecule perspectives on the allosteric link between ligand- and nucleotide-binding pockets that shed new light on the G-protein activation mechanism.
[Mh] Termos MeSH primário: Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Receptores Adrenérgicos beta 2/metabolismo
Imagem Individual de Molécula
[Mh] Termos MeSH secundário: Agonistas de Receptores Adrenérgicos beta 2/química
Agonistas de Receptores Adrenérgicos beta 2/metabolismo
Agonistas de Receptores Adrenérgicos beta 2/farmacologia
Sítio Alostérico
Membrana Celular/metabolismo
Clembuterol/química
Clembuterol/metabolismo
Clembuterol/farmacologia
Ativação Enzimática/efeitos dos fármacos
Epinefrina/química
Epinefrina/metabolismo
Epinefrina/farmacologia
Transferência Ressonante de Energia de Fluorescência
Subunidades alfa Gs de Proteínas de Ligação ao GTP/química
Guanosina Difosfato/metabolismo
Seres Humanos
Cinética
Ligantes
Modelos Moleculares
Movimento/efeitos dos fármacos
Estabilidade Proteica
Receptores Adrenérgicos beta 2/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Adrenergic beta-2 Receptor Agonists); 0 (Ligands); 0 (Receptors, Adrenergic, beta-2); 146-91-8 (Guanosine Diphosphate); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs); XTZ6AXU7KN (Clenbuterol); YKH834O4BH (Epinephrine)
[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/nature22354


  9 / 1883 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28543567
[Au] Autor:Masyuk TV; Masyuk AI; Lorenzo Pisarello M; Howard BN; Huang BQ; Lee PY; Fung X; Sergienko E; Ardecky RJ; Chung TDY; Pinkerton AB; LaRusso NF
[Ad] Endereço:Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
[Ti] Título:TGR5 contributes to hepatic cystogenesis in rodents with polycystic liver diseases through cyclic adenosine monophosphate/Gαs signaling.
[So] Source:Hepatology;66(4):1197-1218, 2017 Oct.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatic cystogenesis in polycystic liver disease is associated with increased levels of cyclic adenosine monophosphate (cAMP) in cholangiocytes lining liver cysts. Takeda G protein receptor 5 (TGR5), a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with polycystic liver disease. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to (1) TGR5 agonists (taurolithocholic acid, oleanolic acid [OA], and two synthetic compounds), (2) a novel TGR5 antagonist (m-tolyl 5-chloro-2-[ethylsulfonyl] pyrimidine-4-carboxylate [SBI-115]), and (3) a combination of SBI-115 and pasireotide, a somatostatin receptor analogue. In vivo, we examined hepatic cystogenesis in OA-treated polycystic kidney rats and after genetic elimination of TGR5 in double mutant TGR5 ;Pkhd1 mice. Compared to control, expression of TGR5 and Gα (but not Gα and Gα ) proteins was increased 2-fold to 3-fold in cystic cholangiocytes in vitro and in vivo. In vitro, TGR5 stimulation enhanced cAMP production, cell proliferation, and cyst growth by ∼40%; these effects were abolished after TGR5 reduction by short hairpin RNA. OA increased cystogenesis in polycystic kidney rats by 35%; in contrast, hepatic cystic areas were decreased by 45% in TGR5-deficient TGR5 ;Pkhd1 mice. TGR5 expression and its colocalization with Gα were increased ∼2-fold upon OA treatment. Levels of cAMP, cell proliferation, and cyst growth in vitro were decreased by ∼30% in cystic cholangiocytes after treatment with SBI-115 alone and by ∼50% when SBI-115 was combined with pasireotide. CONCLUSION: TGR5 contributes to hepatic cystogenesis by increasing cAMP and enhancing cholangiocyte proliferation; our data suggest that a TGR5 antagonist alone or concurrently with somatostatin receptor agonists represents a potential therapeutic approach in polycystic liver disease. (Hepatology 2017;66:1197-1218).
[Mh] Termos MeSH primário: AMP Cíclico/metabolismo
Cistos/metabolismo
Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Hepatopatias/metabolismo
Pirimidinas/uso terapêutico
Receptores Acoplados a Proteínas-G/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal
Animais
Proliferação Celular/efeitos dos fármacos
Cistos/tratamento farmacológico
Avaliação Pré-Clínica de Medicamentos
Quimioterapia Combinada
Seres Humanos
Hepatopatias/tratamento farmacológico
Camundongos
Ácido Oleanólico
Doenças Renais Policísticas/metabolismo
Cultura Primária de Células
Pirimidinas/farmacologia
Ratos
Receptores Acoplados a Proteínas-G/agonistas
Receptores Acoplados a Proteínas-G/antagonistas & inibidores
Receptores Acoplados a Proteínas-G/genética
Somatostatina/análogos & derivados
Somatostatina/farmacologia
Somatostatina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (DZIP1 protein, human); 0 (Gpbar1 protein, rat); 0 (Pyrimidines); 0 (Receptors, G-Protein-Coupled); 0 (m-tolyl 5-chloro-2-(ethylsulfonyl)pyrimidine-4-carboxylate); 51110-01-1 (Somatostatin); 6SMK8R7TGJ (Oleanolic Acid); 98H1T17066 (pasireotide); E0399OZS9N (Cyclic AMP); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29284


  10 / 1883 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28538729
[Au] Autor:Zhang Y; Sun B; Feng D; Hu H; Chu M; Qu Q; Tarrasch JT; Li S; Sun Kobilka T; Kobilka BK; Skiniotis G
[Ad] Endereço:Life Sciences Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
[Ti] Título:Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.
[So] Source:Nature;546(7657):248-253, 2017 06 08.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein G . Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-G complex at near atomic resolution. The peptide is clasped between the N-terminal domain and the transmembrane core of the receptor, and further stabilized by extracellular loops. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the α5-helix of the Ras-like domain of G . These results provide a structural framework for understanding class B GPCR activation through hormone binding.
[Mh] Termos MeSH primário: Microscopia Crioeletrônica
Subunidades alfa Gs de Proteínas de Ligação ao GTP/química
Subunidades alfa Gs de Proteínas de Ligação ao GTP/ultraestrutura
Peptídeo 1 Semelhante ao Glucagon/química
Peptídeo 1 Semelhante ao Glucagon/metabolismo
Receptor do Peptídeo Semelhante ao Glucagon 1/química
Receptor do Peptídeo Semelhante ao Glucagon 1/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo
Receptor do Peptídeo Semelhante ao Glucagon 1/classificação
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo
Modelos Moleculares
Domínios Proteicos
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Glucagon-Like Peptide-1 Receptor); 89750-14-1 (Glucagon-Like Peptide 1); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1038/nature22394



página 1 de 189 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde