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[PMID]:29200982
[Au] Autor:Hamarsland H; Nordengen AL; Nyvik Aas S; Holte K; Garthe I; Paulsen G; Cotter M; Børsheim E; Benestad HB; Raastad T
[Ad] Endereço:Department of Physical Performance, Norwegian School of Sport Sciences, P.O. Box 4014 Ullevål Stadion, 0806 Oslo, Norway.
[Ti] Título:Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial.
[So] Source:J Int Soc Sports Nutr;14:43, 2017.
[Is] ISSN:1550-2783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Protein intake is essential to maximally stimulate muscle protein synthesis, and the amino acid leucine seems to possess a superior effect on muscle protein synthesis compared to other amino acids. Native whey has higher leucine content and thus a potentially greater anabolic effect on muscle than regular whey (WPC-80). This study compared the acute anabolic effects of ingesting 2 × 20 g of native whey protein, WPC-80 or milk protein after a resistance exercise session. Methods: 24 young resistance trained men and women took part in this double blind, randomized, partial crossover, controlled study. Participants received either WPC-80 and native whey ( = 10), in a crossover design, or milk ( = 12). Supplements were ingested immediately (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance exercise. Blood samples and muscle biopsies were collected to measure plasma concentrations of amino acids by gas-chromatography mass spectrometry, muscle phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting, and mixed muscle protein synthesis by use of [ H ]phenylalanine-infusion, gas-chromatography mass spectrometry and isotope-ratio mass spectrometry. Being the main comparison, differences between native whey and WPC-80 were analysed by a one-way ANOVA and comparisons between the whey supplements and milk were analysed by a two-way ANOVA. Results: Native whey increased blood leucine concentrations more than WPC-80 and milk ( < 0.05). Native whey ingestion induced a greater phosphorylation of p70S6K than milk 180 min after exercise ( = 0.03). Muscle protein synthesis rates increased 1-3 h hours after exercise with WPC-80 (0.119%), and 1-5 h after exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1-5 h after exercise with native whey than with milk (0.112% vs. 0.064, = 0.023). Conclusions: Despite higher-magnitude increases in blood leucine concentrations with native whey, it was not superior to WPC-80 concerning effect on muscle protein synthesis and phosphorylation of p70S6K during a 5-h post-exercise period. Native whey increased phosphorylation of p70S6K and muscle protein synthesis rates to a greater extent than milk during the 5-h post exercise period. Trial registration: This study was retrospectively registered at clinicaltrials.gov as NCT02968888.
[Mh] Termos MeSH primário: Suplementos Nutricionais
Leucina/análise
Músculo Esquelético/efeitos dos fármacos
Treinamento de Resistência
Fenômenos Fisiológicos da Nutrição Esportiva
Proteínas do Soro do Leite/química
Proteínas do Soro do Leite/farmacologia
[Mh] Termos MeSH secundário: Estudos Cross-Over
Método Duplo-Cego
Feminino
Voluntários Saudáveis
Seres Humanos
Leucina/farmacologia
Masculino
Proteínas Musculares/biossíntese
Músculo Esquelético/fisiologia
Biossíntese de Proteínas/efeitos dos fármacos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Muscle Proteins); 0 (Whey Proteins); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12970-017-0202-y


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[PMID]:27778166
[Au] Autor:Fan R; Yuan Y; Zhang Q; Zhou XR; Jia L; Liu Z; Yu C; Luo SZ; Chen L
[Ad] Endereço:Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
[Ti] Título:Isoleucine/leucine residues at "a" and "d" positions of a heptad repeat sequence are crucial for the cytolytic activity of a short anticancer lytic peptide.
[So] Source:Amino Acids;49(1):193-202, 2017 01.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Many lytic peptides contain a heptad sequence with leucine or isoleucine residues at "a" and "d" positions. However, their roles in the peptide-induced cytolytic process remain unclear. We have recently reported an anticancer lytic peptide ZXR-2 (FKIGGFIKKLWRSLLA), which contains a shortened zipper-like sequence with Ile/Leu at "a" and "d" positions. To understand the roles of these Ile/Leu residues, a series of analogs were constructed by sequentially replacing the Ile or Leu residue with alanine (Ala). Significant reduction of the cytolytic activity was observed when the Ile (3rd and 7th) and Leu (10th and 14th) residues at the "a" and "d" positions were substituted, while the replacement of the separate Leu (15th) residue had less effect. Based on the quenching of the intrinsic fluorescence of the peptides and their induced surface pressure changes of lipid monolayer, it was conjectured that the peptide ZXR-2 might insert into cell membranes from the C-terminal and to a depth of the W position. Accordingly, I , I , and L residues which mainly exposed in aqueous solution were more responsible for the peptide self-association on cell membranes, while L , together with L , might help peptide insert and anchor to cell membranes. These results are significant to elucidate the crucial roles of such Ile/Leu residues at "a" and "d" positions in peptide-peptide and peptide-membrane interactions to exert the membrane disruption activity of lytic peptides. With further understanding about the structure-activity relationship of lytic peptides, it would be helpful for designing novel anticancer lytic peptides.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Isoleucina/química
Leucina/química
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: 1,2-Dipalmitoilfosfatidilcolina/análogos & derivados
1,2-Dipalmitoilfosfatidilcolina/química
Alanina/química
Sequência de Aminoácidos
Substituição de Aminoácidos
Antineoplásicos/síntese química
Linhagem Celular Tumoral
Membrana Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Colesterol/química
Células HEK293
Células HeLa
Seres Humanos
L-Lactato Desidrogenase/secreção
Lipossomos/química
Peptídeos/síntese química
Fosfatidilserinas/química
Engenharia de Proteínas
Estrutura Secundária de Proteína
Eletricidade Estática
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Liposomes); 0 (Peptides); 0 (Phosphatidylserines); 04Y7590D77 (Isoleucine); 2644-64-6 (1,2-Dipalmitoylphosphatidylcholine); 3036-82-6 (dipalmitoylphosphatidylserine); 319X2NFW0A (colfosceril palmitate); 97C5T2UQ7J (Cholesterol); EC 1.1.1.27 (L-Lactate Dehydrogenase); GMW67QNF9C (Leucine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-016-2350-9


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[PMID]:29336152
[Au] Autor:Fu B; Xu T; Cui Z; Ng HL; Wang K; Li J; Li QX
[Ad] Endereço:Beijing Key Laboratory of Biodiversity and Organic Farming, College of Resources and Environmental Sciences, China Agricultural University , 2 Yuanmingyuan West Road, Beijing 100193, China.
[Ti] Título:Mutation of Phenylalanine-223 to Leucine Enhances Transformation of Benzo[a]pyrene by Ring-Hydroxylating Dioxygenase of Sphingobium sp. FB3 by increasing Accessibility of the Catalytic Site.
[So] Source:J Agric Food Chem;66(5):1206-1213, 2018 Feb 07.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Burning of agricultural biomass generates polycyclic aromatic hydrocarbons (PAHs) including the carcinogen benzo[a]pyrene, of which the catabolism is primarily initiated by a ring-hydroxylating dioxygenase (RHD). This study explores catalytic site accessibility and its role in preferential catabolism of some PAHs over others. The genes flnA1f, flnA2f, flnA3, and flnA4, encoding the oxygenase α and ß subunits, ferredoxin, and ferredoxin reductase, respectively, of the RHD enzyme complex (FlnA) were cloned from Sphingobium sp. FB3 and coexpressed in E. coli BL21. The FlnA effectively transformed fluoranthene but not benzo[a]pyrene. Substitution of the bulky phenylalanine-223 by leucine reduces the steric constraint in the substrate entrance to make the catalytic site of FlnA more accessible to large substrates, as visualized by 3D modeling, and allows the FlnA mutant to efficiently transform benzo[a]pyrene. Accessibility of the catalytic site to PAHs is a mechanism of RHD substrate specificity. The results shed light on why some PAHs are more recalcitrant than others.
[Mh] Termos MeSH primário: Benzo(a)pireno/metabolismo
Domínio Catalítico/fisiologia
Dioxigenases/metabolismo
Leucina/genética
Mutação
Fenilalanina/genética
[Mh] Termos MeSH secundário: Biodegradação Ambiental
Clonagem Molecular
Dioxigenases/genética
Escherichia coli/genética
Fluorenos/metabolismo
Expressão Gênica
Hidroxilação
Leucina/química
Fenilalanina/química
Hidrocarbonetos Aromáticos Policíclicos/metabolismo
Proteobactérias/enzimologia
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorenes); 0 (Polycyclic Aromatic Hydrocarbons); 3417WMA06D (Benzo(a)pyrene); 360UOL779Z (fluoranthene); 47E5O17Y3R (Phenylalanine); EC 1.13.11.- (Dioxygenases); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b05018


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[PMID]:29293584
[Au] Autor:Olivan-Viguera A; Garcia-Otin AL; Lozano-Gerona J; Abarca-Lachen E; Garcia-Malinis AJ; Hamilton KL; Gilaberte Y; Pueyo E; Köhler R
[Ad] Endereço:Biosignal Interpretation and Computational Simulation (BSICoS), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
[Ti] Título:Pharmacological activation of TRPV4 produces immediate cell damage and induction of apoptosis in human melanoma cells and HaCaT keratinocytes.
[So] Source:PLoS One;13(1):e0190307, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: TRPV4 channels are calcium-permeable cation channels that are activated by several physicochemical stimuli. Accordingly, TRPV4 channels have been implicated in the regulation of osmosensing, mechanotransduction, thermosensation, and epithelial/endothelial barrier functions. Whether TRPV4 is also mechanistically implicated in melanoma cell proliferation is not clear. Here, we hypothesized that TRPV4 is expressed in human melanoma and that pharmacological activation interferes with cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS: TRPV4 functions were studied in melanoma cell lines (A375, SK-MEL-28, MKTBR), immortalized non-cancer keratinocytes (HaCaT), and murine 3T3 fibroblasts by patch-clamp, qRT-PCR, intracellular calcium measurements, cell proliferation, and flow cytometric assays of apoptosis and cell cycle. The selective TRPV4-activator, GSK1016790A, elicited non-selective cation currents with TRPV4-typical current-voltage-relationship in all cell lines. GSK1016790A-induced currents were blocked by the TRPV4-blocker, HC067047. TRPV4 mRNA expression was demonstrated by qRT-PCR. In A375 cells, TRPV4 activation was frequently paralleled by co-activation of calcium/calmodulin-regulated KCa3.1 channels. Light microscopy showed that TRPV4-activation produced rapid cellular disarrangement, nuclear densification, and detachment of a large fraction of all melanoma cell lines and HaCaT cells. TRPV4-activation induced apoptosis and drastically inhibited A375 and HaCaT proliferation that could be partially prevented by HC067047. CONCLUSIONS/SIGNIFICANCE: Our study showed that TRPV4 channels were functionally expressed in human melanoma cell lines and in human keratinocytes. Pharmacological TRPV4 activation in human melanoma cells and keratinocytes caused severe cellular disarrangement, necrosis and apoptosis. Pharmacological targeting of TRPV4 could be an alternative or adjuvant therapeutic strategy to treat melanoma progression and other proliferative skin disorders.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Queratinócitos/patologia
Melanoma/patologia
Canais de Cátion TRPV/agonistas
[Mh] Termos MeSH secundário: Células 3T3
Animais
Cálcio/metabolismo
Ciclo Celular
Linhagem Celular
Linhagem Celular Tumoral
Citometria de Fluxo
Seres Humanos
Queratinócitos/metabolismo
Leucina/análogos & derivados
Leucina/farmacologia
Melanoma/metabolismo
Camundongos
Técnicas de Patch-Clamp
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide); 0 (Sulfonamides); 0 (TRPV Cation Channels); 0 (TRPV4 protein, human); GMW67QNF9C (Leucine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190307


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[PMID]:29227681
[Au] Autor:Duan Y; Li F; Guo Q; Wang W; Zhang L; Wen C; Chen X; Yin Y
[Ad] Endereço:Laboratory of Animal Nutritional Physiology and Metabolic Process, Institute of Subtropical Agriculture Chinese Academy of Sciences; Key Laboratory of Agro-ecological Processes in Subtropical Region; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Scientifi
[Ti] Título:ß-Hydroxy-ß-methyl Butyrate Is More Potent Than Leucine in Inhibiting Starvation-Induced Protein Degradation in C2C12 Myotubes.
[So] Source:J Agric Food Chem;66(1):170-176, 2018 Jan 10.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leucine (Leu) and its metabolites α-ketoisocaproate (KIC) and ß-hydroxy-ß-methyl butyrate (HMB) are potent regulators of protein turnover. The aim of this study was to compare the inhibitory effects of Leu, KIC, and HMB on protein degradation and to investigate the mechanisms involved. The results showed that the inhibitory effect of HMB (0.38 ± 0.04) was more potent than that of Leu (0.76 ± 0.04) and KIC (0.56 ± 0.04, P < 0.01), and was significantly abolished in the presence of LY294002 (1.48 ± 0.02) and rapamycin (1.96 ± 0.02, P < 0.01). In the presence of insulin, the inhibitory effect of HMB (0.34 ± 0.03) was still more effective than that of Leu (0.60 ± 0.04) and KIC (0.57 ± 0.08, P < 0.05). Interestingly, LY294002 treatment markedly attenuated the effect of HMB, while rapamycin treatment failed to exert the same effect. Thus, HMB appears to be more potent than Leu and KIC in inhibiting protein degradation in the absence or presence of insulin, and this inhibitory effect may be dependent on PI3K/Akt signaling pathway regardless of insulin, and mTOR signaling was only involved in this effect of HMB in the absence of insulin.
[Mh] Termos MeSH primário: Leucina/farmacologia
Fibras Musculares Esqueléticas/efeitos dos fármacos
Proteólise/efeitos dos fármacos
Valeratos/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Insulina/farmacologia
Cetoácidos/farmacologia
Camundongos
Fibras Musculares Esqueléticas/metabolismo
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Proteínas Ligases SKP Culina F-Box/genética
Proteínas Ligases SKP Culina F-Box/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Proteínas com Motivo Tripartido/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Keto Acids); 0 (Muscle Proteins); 0 (Tripartite Motif Proteins); 0 (Valerates); 3F752311CD (beta-hydroxyisovaleric acid); 816-66-0 (alpha-ketoisocaproic acid); EC 2.3.2.27 (Fbxo32 protein, mouse); EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases); EC 2.3.2.27 (Trim63 protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, mouse); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04841


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[PMID]:28448887
[Au] Autor:Wang H; Barona D; Oladepo S; Williams L; Hoe S; Lechuga-Ballesteros D; Vehring R
[Ad] Endereço:Department of Mechanical Engineering, University of Alberta, Edmonton, AB T6G 2G8, Canada.
[Ti] Título:Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders.
[So] Source:J Pharm Biomed Anal;141:180-191, 2017 Jul 15.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A new macro-Raman system equipped with a motorized translational sample stage and low-frequency shift capabilities was developed for bulk composition and homogeneity analysis of multi-component pharmaceutical powders. Different sampling methods including single spot and scanning measurement were compared. It was found that increasing sample volumes significantly improved the precision of quantitative composition analysis, especially for poorly mixed powders. The multi-pass cavity of the macro-Raman system increased effective sample volumes by 20 times from the sample volume defined by the collection optics, i.e., from 0.02µL to about 0.4µL. A stochastic model simulating the random sampling process of polydisperse microparticles was used to predict the sampling errors for a specific sample volume. Comparison of fluticasone propionate mass fractions of the commercial products Flixotide 250 and Seretide 500 simulated for different sampling volumes with experimentally measured compositions verified that the effective sample volume of a single point macro-Raman measurement in the multi-pass cavity of this instrument was between 0.3µL and 0.5µL. The macro-Raman system was also successfully used for blend uniformity analysis. It was concluded that demixing occurred in the binary mixture of l-leucine and d-mannitol from the observation that the sampling errors indicated by the standard deviations of measured leucine mass fractions increased during mixing, and the standard deviation values were all larger than the theoretical lower limit determined by the simulation. Since sample volume was shown to have a significant impact on measured homogeneity characteristics, it was concluded that powder homogeneity analysis results, i.e., the mean of individual test results and absolute and relative standard deviations, must be presented together with the effective sample volumes of the applied testing techniques for any measurement of powder homogeneity to be fully meaningful.
[Mh] Termos MeSH primário: Análise Espectral Raman
[Mh] Termos MeSH secundário: Química Farmacêutica
Fluticasona
Leucina
Manitol
Preparações Farmacêuticas
Pós
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations); 0 (Powders); 3OWL53L36A (Mannitol); CUT2W21N7U (Fluticasone); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


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[PMID]:29202398
[Au] Autor:Jiang Y; Li X; Hou J; Huang Y; Wang X; Jia Y; Wang Q; Xu W; Zhang J; Zhang Y
[Ad] Endereço:Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, PR China.
[Ti] Título:Synthesis and biological characterization of ubenimex-fluorouracil conjugates for anti-cancer therapy.
[So] Source:Eur J Med Chem;143:334-347, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Previously a novel ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified and validated as a potent CD13 inhibitor with marked in vitro and in vivo antitumor potency. Herein, further structural modifications of the linker part of BC-01 was carried out to get more potent and stable ubenimex-fluorouracil conjugates. It was striking that most of these conjugates showed even more potent CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor ubenimex. One representative compound 12a displayed significant in vitro anti-proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13 cell elimination effects. In vitro stability and in vivo pharmacokinetic study revealed that compound 12a could release ubenimex and 5-FU slowly, which could act as a mutual prodrug of ubenimex and 5-FU. Compared with 5-FU or 5-FU plus ubenimex, 12a exhibited superior in vivo antitumor growth efficiency, even in our mice model of 5-FU-resistant liver cancer. Moreover, 12a exhibited more potent in vivo anti-metastasis and lifespan extension effects compared to the approved 5-FU prodrug capecitabine. Collectively, these results suggest that further optimization and evaluation of 12a as a promising anticancer candidate are warranted to develop effective therapeutic agents for human liver cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Fluoruracila/farmacologia
Leucina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Feminino
Fluoruracila/química
Seres Humanos
Leucina/química
Leucina/farmacologia
Camundongos
Camundongos Endogâmicos
Estrutura Molecular
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/patologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); GMW67QNF9C (Leucine); I0J33N5627 (ubenimex); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE


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[PMID]:28462835
[Au] Autor:Gao M; Wang M; Meyer JA; Peters JS; Zarrinmayeh H; Territo PR; Hutchins GD; Zheng QH
[Ad] Endereço:Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
[Ti] Título:Synthesis and preliminary biological evaluation of [ C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CX CR1).
[So] Source:Bioorg Med Chem Lett;27(12):2727-2730, 2017 06 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [ C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([ C]5) was prepared from the acid precursor with [ C]CH OTf through O-[ C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [ C]CO and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/µmol with a total synthesis time of ∼40-min from EOB. The radioligand depletion experiment of [ C]5 did not display specific binding to CX CR1, and the competitive binding assay of ligand 5 found much lower CX CR1 binding affinity.
[Mh] Termos MeSH primário: Leucina/análogos & derivados
Pirimidinas/farmacologia
Receptores de Quimiocinas/antagonistas & inibidores
Tiazóis/farmacologia
[Mh] Termos MeSH secundário: Receptor 1 de Quimiocina CX3C
Isótopos de Carbono
Relação Dose-Resposta a Droga
Seres Humanos
Leucina/síntese química
Leucina/química
Leucina/farmacologia
Ligantes
Estrutura Molecular
Pirimidinas/síntese química
Pirimidinas/química
Receptores de Quimiocinas/metabolismo
Relação Estrutura-Atividade
Tiazóis/síntese química
Tiazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (CX3C Chemokine Receptor 1); 0 (CX3CR1 protein, human); 0 (Carbon Isotopes); 0 (Ligands); 0 (Pyrimidines); 0 (Receptors, Chemokine); 0 (Thiazoles); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29045496
[Au] Autor:Revel A; Jarzaguet M; Peyron MA; Papet I; Hafnaoui N; Migné C; Mosoni L; Polakof S; Savary-Auzeloux I; Rémond D; Dardevet D
[Ad] Endereço:Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, PFEM, MetaboHUB-Clermont, CRNH Auvergne, Clermont-Ferrand, France.
[Ti] Título:At same leucine intake, a whey/plant protein blend is not as effective as whey to initiate a transient post prandial muscle anabolic response during a catabolic state in mini pigs.
[So] Source:PLoS One;12(10):e0186204, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Muscle atrophy has been explained by an anabolic resistance following food intake and an increase of dietary protein intake is recommended. To be optimal, a dietary protein has to be effective not only to initiate but also to prolong a muscle anabolic response in a catabolic state. To our knowledge, whether or not a dairy or a dairy/plant protein blend fulfills these criterions is unknown in a muscle wasting situation. OBJECTIVE: Our aim was, in a control and a catabolic state, to measure continuously muscle anabolism in term of intensity and duration in response to a meal containing casein (CAS), whey (WHEY) or a whey/ plant protein blend (BLEND) and to evaluate the best protein source to elicit the best post prandial anabolism according to the physio-pathological state. METHODS: Adult male Yucatan mini pigs were infused with U-13C-Phenylalanine and fed either CAS, WHEY or BLEND. A catabolic state was induced by a glucocorticoid treatment for 8 days (DEX). Muscle protein synthesis, proteolysis and balance were measured with the hind limb arterio-venous differences technique. Repeated time variance analysis were used to assess significant differences. RESULTS: In a catabolic situation, whey proteins were able to initiate muscle anabolism which remained transient in contrast to the stimulated muscle protein accretion with WHEY, CAS or BLEND in healthy conditions. Despite the same leucine intake compared to WHEY, BLEND did not restore a positive protein balance in DEX animals. CONCLUSIONS: Even with WHEY, the duration of the anabolic response was not optimal and has to be improved in a catabolic state. The use of BLEND remained of lower efficiency even at same leucine intake than whey.
[Mh] Termos MeSH primário: Anabolizantes/administração & dosagem
Caseínas/administração & dosagem
Leucina/metabolismo
Atrofia Muscular/dietoterapia
Proteínas de Vegetais Comestíveis/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Ingestão de Alimentos
Glucocorticoides/administração & dosagem
Metabolismo/efeitos dos fármacos
Músculo Esquelético/efeitos dos fármacos
Músculo Esquelético/metabolismo
Atrofia Muscular/metabolismo
Atrofia Muscular/patologia
Período Pós-Prandial/efeitos dos fármacos
Suínos
Porco Miniatura
Soro do Leite/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anabolic Agents); 0 (Caseins); 0 (Glucocorticoids); 0 (Vegetable Proteins); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186204


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[PMID]:28982725
[Au] Autor:Mitchell WK; Phillips BE; Hill I; Greenhaff P; Lund JN; Williams JP; Rankin D; Wilkinson DJ; Smith K; Atherton PJ
[Ad] Endereço:MRC-ARUK Centre for Musculoskeletal Ageing Research and NIHR Nottingham BRC, School of Medicine, Royal Derby Hospital, University of Nottingham, U.K.
[Ti] Título:Human skeletal muscle is refractory to the anabolic effects of leucine during the postprandial muscle-full period in older men.
[So] Source:Clin Sci (Lond);131(21):2643-2653, 2017 Nov 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men. During C -phenylalanine infusion, 16 men (∼70 years) consumed 15 g of EAA with ( =8, FED + LEU) or without ( =8, FED) 3 g of leucine top-up 90 min later. Repeated blood and muscle sampling permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling including mTOR complex 1 (mTORC1) substrates, cellular ATP and phosphorylocreatine, and MPS. Oral EAA achieved rapid insulinemia (12.5 iU·ml 25 min post-feed), essential aminoacidemia (3000 µM, 45-65 min post-feed), and activation of mTORC1 signaling. Leucine top-up prolonged plasma EAA (2800 µM, 135 min) and leucine availability (1050 µM, 135 min post-feed). Fasting FSRs of 0.046 and 0.056%·h (FED and FED + LEU respectively) increased to 0.085 and 0.085%·h 90-180 min post-feed and returned to basal rates after 180 min in both groups. Phosphorylation of mTORC1 substrates returned to fasting levels 240 min post-feed in both groups. Feeding had limited effect on muscle high-energy phosphates, but did induce eukaryotic elongation factor 2 (eEF2) phosphorylation. We demonstrate the refractoriness of muscle to nutrient-led anabolic stimulation in the postprandial period; thus, leucine supplements should be taken outside of meals, or with meals containing suboptimal protein in terms of either amount or EAA composition.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Anabolizantes/administração & dosagem
Suplementos Nutricionais
Metabolismo Energético/efeitos dos fármacos
Leucina/administração & dosagem
Músculo Esquelético/efeitos dos fármacos
Período Pós-Prandial
Biossíntese de Proteínas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Fatores Etários
Idoso
Envelhecimento/sangue
Anabolizantes/sangue
Seres Humanos
Insulina/sangue
Leucina/sangue
Masculino
Alvo Mecanístico do Complexo 1 de Rapamicina
Complexos Multiproteicos/metabolismo
Músculo Esquelético/metabolismo
Fosfocreatina/metabolismo
Fosforilação
Estudos Prospectivos
Fatores Sexuais
Serina-Treonina Quinases TOR/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anabolic Agents); 0 (Insulin); 0 (Multiprotein Complexes); 020IUV4N33 (Phosphocreatine); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); GMW67QNF9C (Leucine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1042/CS20171230



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