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[PMID]:28469997
[Au] Autor:Zhao M; Zhang L; Lv S; Zhang C; Wang L; Chen H; Zhou Y; Lou J
[Ad] Endereço:Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghai, China.
[Ti] Título:IQGAP1 Mediates Hcp1-Promoted Meningitis by Stimulating the MAPK Pathway.
[So] Source:Front Cell Infect Microbiol;7:132, 2017.
[Is] ISSN:2235-2988
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/farmacologia
Escherichia coli/metabolismo
Meningite devida a Escherichia coli/metabolismo
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
Fatores de Virulência/farmacologia
Proteínas Ativadoras de ras GTPase/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Encéfalo
Butadienos/antagonistas & inibidores
Linhagem Celular
Citocinas/análise
Modelos Animais de Doenças
Células Endoteliais/efeitos dos fármacos
Seres Humanos
Meningite devida a Escherichia coli/tratamento farmacológico
Camundongos
Camundongos Endogâmicos C57BL
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Nitrilos/antagonistas & inibidores
Fosforilação
RNA Interferente Pequeno
Transdução de Sinais
Ubiquitina-Proteína Ligases
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Butadienes); 0 (Cytokines); 0 (Escherichia coli Proteins); 0 (HCP1 protein, E coli); 0 (IQ motif containing GTPase activating protein 1); 0 (Nitriles); 0 (RNA, Small Interfering); 0 (U 0126); 0 (Virulence Factors); 0 (ras GTPase-Activating Proteins); EC 2.3.2.26 (SMURF1 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.3389/fcimb.2017.00132


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[PMID]:29329665
[Au] Autor:Wang Y; Yu YX; Luan Y; An J; Yin DG; Zhang XY
[Ad] Endereço:School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
[Ti] Título:Bioactivation of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3-butadiene, by rat liver microsomes.
[So] Source:Chem Biol Interact;282:36-44, 2018 Feb 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:1-Chloro-2-hydroxy-3-butene (CHB) is an in vitro metabolite of 1,3-butadiene, a rodent/human carcinogen. To search for an approach detecting CHB in vivo, it is vital to obtain a full understanding of CHB metabolism. Previously, we demonstrated that CHB was bioactivated to 1-chloro-3-buten-2-one (CBO) by alcohol dehydrogenase. However, CHB metabolism by cytochrome P450s has not been reported. Thus, in the present study, CHB metabolism by rat liver microsomes was investigated. The results showed that CHB was converted to 1-chloro-3,4-epoxy-2-butanol (CEB) and CBO. 4-Methylpyrazole, a cytochrome P450 2E1-specific inhibitor, inhibited the formation of both CEB and CBO, while 1-benzylimidazole, a generic cytochrome P450 inhibitor, completely abolished the formation of CEB and CBO, suggesting that CHB metabolism was mediated by cytochrome P450s. Because the molecules have two chiral centers, CEB was detected as two stereoisomers, which were designated D-CEB and M-CEB, and were characterized as (2S,3R)-/(2R,3S)-CEB and (2R,3R)-/(2S,3S)-CEB, respectively. The amounts of M-CEB were more than those of D-CEB by 50-80%. The amounts of CEB and CBO increased linearly over time from 10 (or 20 min for CBO) to 50 min. CHB metabolism followed Michaelis-Menten kinetics; the K and V values were determined to be 6.4 ±â€¯0.7 mM and 0.10 ±â€¯0.01 nmol/min/mg protein for D-CEB, 4.2 ±â€¯0.5 mM and 0.16 ±â€¯0.01 nmol/min/mg protein for M-CEB, and 4.0 ±â€¯0.5 mM and 4.6 ±â€¯0.5 nmol/min/mg protein for CBO, respectively. Thus, CBO was the dominant product of CHB metabolism. Moreover, CEB was genotoxic at ≥ 50 µM as evaluated by the comet assay. Collectively, the data showed that CHB could be bioactivated to CEB and CBO by cytochrome P450s with CBO being the predominant product. Thus, the formation of CEB and CBO can be used as evidence of CHB production. The products may also play a role in toxicity of CHB.
[Mh] Termos MeSH primário: Butadienos/metabolismo
Butanóis/metabolismo
Microssomos Hepáticos/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinógenos/metabolismo
Ensaio Cometa/métodos
Sistema Enzimático do Citocromo P-450/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Butanols); 0 (Carcinogens); 671-56-7 (1-chloro-2-hydroxy-3-butene); 9035-51-2 (Cytochrome P-450 Enzyme System); JSD5FGP5VD (1,3-butadiene)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE


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[PMID]:29195373
[Au] Autor:Szabra D; Prokopiuk A; Mikolajczyk J; Ligor T; Buszewski B; Bielecki Z
[Ad] Endereço:Institute of Optoelectronics, Military University of Technology, 2 Kaliskiego St., 00-908 Warsaw, Poland.
[Ti] Título:Air sampling unit for breath analyzers.
[So] Source:Rev Sci Instrum;88(11):115006, 2017 Nov.
[Is] ISSN:1089-7623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The paper presents a portable breath sampling unit (BSU) for human breath analyzers. The developed unit can be used to probe air from the upper airway and alveolar for clinical and science studies. The BSU is able to operate as a patient interface device for most types of breath analyzers. Its main task is to separate and to collect the selected phases of the exhaled air. To monitor the so-called I, II, or III phase and to identify the airflow from the upper and lower parts of the human respiratory system, the unit performs measurements of the exhaled CO (ECO ) in the concentration range of 0%-20% (0-150 mm Hg). It can work in both on-line and off-line modes according to American Thoracic Society/European Respiratory Society standards. A Tedlar bag with a volume of 5 dm is mounted as a BSU sample container. This volume allows us to collect ca. 1-25 selected breath phases. At the user panel, each step of the unit operation is visualized by LED indicators. This helps us to regulate the natural breathing cycle of the patient. There is also an operator's panel to ensure monitoring and configuration setup of the unit parameters. The operation of the breath sampling unit was preliminarily verified using the gas chromatography/mass spectrometry (GC/MS) laboratory setup. At this setup, volatile organic compounds were extracted by solid phase microextraction. The tests were performed by the comparison of GC/MS signals from both exhaled nitric oxide and isoprene analyses for three breath phases. The functionality of the unit was proven because there was an observed increase in the signal level in the case of the III phase (approximately 40%). The described work made it possible to construct a prototype of a very efficient breath sampling unit dedicated to breath sample analyzers.
[Mh] Termos MeSH primário: Testes Respiratórios/instrumentação
Cromatografia Gasosa-Espectrometria de Massas
Microextração em Fase Sólida
[Mh] Termos MeSH secundário: Butadienos/análise
Hemiterpenos/análise
Seres Humanos
Óxido Nítrico/análise
Pentanos/análise
Compostos Orgânicos Voláteis/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Hemiterpenes); 0 (Pentanes); 0 (Volatile Organic Compounds); 0A62964IBU (isoprene); 31C4KY9ESH (Nitric Oxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171203
[St] Status:MEDLINE
[do] DOI:10.1063/1.4995502


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[PMID]:29388547
[Au] Autor:Du K; Zhou M; Li Q; Liu XZ
[Ad] Endereço:Department of clinical laboratory, The first clinical medical college of Yangtze university and the first people's hospital of Jingzhou, Jingzhou 434000, Hubei Province, PR China.
[Ti] Título:Chlamydia trachomatis inhibits the production of pro-inflammatory cytokines in human PBMCs through induction of IL-10.
[So] Source:J Med Microbiol;67(2):240-248, 2018 Feb.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Previous research demonstrated that IL-10 was up-regulated in Chlamydia trachomatis-infected cells and that exogenous IL-10 was able to inhibit the secretion of pro-inflammatory cytokines by infected cells. However, the mechanisms are not well understood. The aim of this study was to investigate the mechanisms for up-regulation of IL-10 and inhibition of pro-inflammatory cytokine secretion in C. trachomatis-stimulated peripheral blood mononuclear cells (PBMCs). METHODOLOGY: Human PBMCs were isolated from the blood of healthy human donors by standard Ficoll-Hypaque density gradient centrifugation. Cells were exposed to C. trachomatis in the presence or absence of MEK inhibitor U0126, the p38 inhibitor SB203580, the STAT3 inhibitor Ruxolitinib or anti-human IL-10 antibody. Cytokines were measured from culture supernatants using ELISA kits. Cells were harvested for real-time quantitative PCR to determine IL-10 mRNA levels and for Western blot assay to detect the expression of ERK1/2, p-ERK1/2, p38, p-p38, STAT3 and p-STAT3. RESULTS: Both mRNA and protein levels of IL-10 were up-regulated in stimulated cells, and the production of IL-10 was reduced when cells were treated with U0126 or SB203580. The expression of cytokines IL-6, IL-8 and TNF-α was enhanced in stimulated cells treated with anti-human IL-10 antibody. Moreover, neutralization of IL-10 resulted in a significant decrease of phosphorylated STAT3 in stimulated cells. Ruxolitinib caused a significant increase in the production of IL-6, IL-8 and TNF-α in stimulated cells. CONCLUSION: IL-10 is up-regulated in an ERK- and p38-dependent fashion in stimulated human PBMCs. IL-10 inhibits the production of pro-inflammatory cytokines by activating the JAK/STAT signalling pathway.
[Mh] Termos MeSH primário: Chlamydia trachomatis/imunologia
Chlamydia trachomatis/patogenicidade
Citocinas/biossíntese
Interleucina-10/biossíntese
Leucócitos Mononucleares/imunologia
[Mh] Termos MeSH secundário: Butadienos/farmacologia
Chlamydia trachomatis/fisiologia
Inibidores Enzimáticos/farmacologia
Seres Humanos
Imidazóis/farmacologia
Inflamação
Interleucina-10/genética
Interleucina-10/imunologia
Interleucina-6/biossíntese
Interleucina-8/biossíntese
Leucócitos Mononucleares/efeitos dos fármacos
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Nitrilos/farmacologia
Pirazóis/farmacologia
Piridinas/farmacologia
Reação em Cadeia da Polimerase em Tempo Real
Fator de Transcrição STAT3/genética
Fator de Transcrição STAT3/metabolismo
Fator de Necrose Tumoral alfa/biossíntese
Regulação para Cima
Proteínas Quinases p38 Ativadas por Mitógeno/genética
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Cytokines); 0 (Enzyme Inhibitors); 0 (IL10 protein, human); 0 (INCB018424); 0 (Imidazoles); 0 (Interleukin-6); 0 (Interleukin-8); 0 (Nitriles); 0 (Pyrazoles); 0 (Pyridines); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (Tumor Necrosis Factor-alpha); 0 (U 0126); 130068-27-8 (Interleukin-10); EC 2.7.11.24 (MAPK1 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); OU13V1EYWQ (SB 203580)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000672


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[PMID]:29190630
[Au] Autor:Chen CM; Hsieh SC; Lin CL; Lin YS; Tsai JP; Hsieh YH
[Ad] Endereço:Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
[Ti] Título:Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity.
[So] Source:Cell Physiol Biochem;44(4):1460-1470, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells. METHODS: Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography. RT-qPCR and a luciferase assay were used to examine the transcriptional activity of MMP-9. RESULTS: α-mangostin inhibited the migration and invasion of RCC cells in a dose-dependent manner, but had no evident cytotoxic effects. Treatment of 786-O cells with α-mangostin inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor (U0126) enhanced the inhibitory effects of α-mangostin on cell migration and invasion, and the phosphorylation of ERK and MEK. Moreover, α-mangostin inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP-9 promoter, and these suppressive effects were further enhanced by U0126. CONCLUSIONS: Our results suggest that α-mangostin suppresses cell migration and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic agent against human renal cell carcinoma.
[Mh] Termos MeSH primário: Anticarcinógenos/toxicidade
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
MAP Quinase Quinase Quinases/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Transdução de Sinais/efeitos dos fármacos
Transcrição Genética/efeitos dos fármacos
Xantonas/toxicidade
[Mh] Termos MeSH secundário: Anticarcinógenos/química
Butadienos/farmacologia
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Neoplasias Renais/metabolismo
Neoplasias Renais/patologia
Metaloproteinase 2 da Matriz/metabolismo
Metaloproteinase 9 da Matriz/genética
Nitrilos/farmacologia
Xantonas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticarcinogenic Agents); 0 (Butadienes); 0 (Nitriles); 0 (U 0126); 0 (Xanthones); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 2.7.11.25 (MAP Kinase Kinase Kinases); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (Matrix Metalloproteinase 9); U6RIV93RU1 (mangostin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1159/000485582


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[PMID]:27770611
[Au] Autor:Wang Y; Hao X; Yang J; Li J; Zhang M
[Ad] Endereço:State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.
[Ti] Título:CREB activity is required for luteinizing hormone-induced the expression of EGF-like factors.
[So] Source:Mol Reprod Dev;83(12):1116-1127, 2016 Dec.
[Is] ISSN:1098-2795
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A surge of luteinizing hormone (LH) from the pituitary gland induces the expression of the epidermal growth factor (EGF)-like factors, which triggers oocyte maturation, cumulus expansion, and ovulation. How LH induces EGF-like factor expression is unclear. In the present study, a rapid increase of phosphorylated cAMP response element binding protein (CREB) was observed after the activation of LH receptor by human chorionic gonadotropin. Large antral follicles from equine chorionic gonadotropin-primed mice were cultured in medium with LH to stimulate the expression of EGF-like factors. CREB phosphorylation was increased in granulosa cells; conversely KG-501, a CREB functional inhibitor, significantly reduced LH-induced gene expression of EGF-like factors, oocyte meiotic resumption, and cumulus cell expansion. Reduction of CREB expression by Creb siRNA also repressed LH-induced expression of EGF-like factors in cultured granulosa cells. Inactivation of mitogen-activated protein kinase (MAPK3/1) by U0126 inhibited LH-induced CREB phosphorylation and EGF-like factors gene expression, whereas the activation of LH receptor increased Akt/protein kinase B phosphorylation, which is involved in LH-induced CREB phosphorylation and the expression of EGF-like factors. Thus, LH induces MAPK3/1 and Akt activation, both of which are required for the CREB-promoted expression of EGF-like factors in granulosa cells. Mol. Reprod. Dev. 83: 1116-1127, 2016. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Fator de Crescimento Epidérmico/biossíntese
Regulação da Expressão Gênica/efeitos dos fármacos
Células da Granulosa/metabolismo
Hormônio Luteinizante/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Butadienos/farmacologia
Feminino
Células da Granulosa/citologia
Camundongos
Camundongos Endogâmicos ICR
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Nitrilos/farmacologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Creb1 protein, mouse); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Nitriles); 0 (U 0126); 62229-50-9 (Epidermal Growth Factor); 9002-67-9 (Luteinizing Hormone); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Mapk1 protein, mouse); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171215
[Lr] Data última revisão:
171215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1002/mrd.22753


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[PMID]:27776993
[Au] Autor:Cai HY; Wang ZJ; Hölscher C; Yuan L; Zhang J; Sun P; Li J; Yang W; Wu MN; Qi JS
[Ad] Endereço:Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan 030001, China.
[Ti] Título:Lixisenatide attenuates the detrimental effects of amyloid ß protein on spatial working memory and hippocampal neurons in rats.
[So] Source:Behav Brain Res;318:28-35, 2017 02 01.
[Is] ISSN:1872-7549
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer's disease (AD), which is most likely linked to impairments of insulin signaling in the brain. Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, facilitates insulin signaling and has neuroprotective properties. We previously reported the protective effects of lixisenatide on memory formation and synaptic plasticity. Here, we describe additional key neuroprotective properties of lixisenatide and its possible molecular and cellular mechanisms against AD-related impairments in rats. The results show that lixisenatide effectively alleviated amyloid ß protein (Aß) 25-35-induced working memory impairment, reversed Aß25-35-triggered cytotoxicity on hippocampal cell cultures, and prevented against Aß25-35-induced suppression of the Akt-MEK1/2 signaling pathway. Lixisenatide also reduced the Aß25-35 acute application induced intracellular calcium overload, which was abolished by U0126, a specific MEK1/2 inhibitor. These results further confirmed the neuroprotective and cytoprotective action of lixisenatide against Aß-induced impairments, suggesting that the protective effects of lixisenatide may involve the activation of the Akt-MEK1/2 signaling pathway and the regulation of intracellular calcium homeostasis.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/antagonistas & inibidores
Hipocampo/efeitos dos fármacos
Memória de Curto Prazo/efeitos dos fármacos
Fragmentos de Peptídeos/antagonistas & inibidores
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/farmacologia
Animais
Butadienos/farmacologia
Cálcio/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Aprendizagem em Labirinto/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Fármacos Neuroprotetores/farmacologia
Nitrilos/farmacologia
Fragmentos de Peptídeos/farmacologia
Cultura Primária de Células
Ratos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Butadienes); 0 (Neuroprotective Agents); 0 (Nitriles); 0 (Peptide Fragments); 0 (Peptides); 0 (U 0126); 0 (amyloid beta-protein (25-35)); 74O62BB01U (lixisenatide); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171202
[Lr] Data última revisão:
171202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:28972999
[Au] Autor:Mohammed RH; Anderton H; Brameld JM; Sweetman D
[Ad] Endereço:School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
[Ti] Título:Effects of insulin like growth factors on early embryonic chick limb myogenesis.
[So] Source:PLoS One;12(10):e0185775, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Limb muscles derive from pax3 expressing precursor cells that migrate from the hypaxial somite into the developing limb bud. Once there they begin to differentiate and express muscle determination genes such as MyoD. This process is regulated by a combination of inductive or inhibitory signals including Fgf18, retinoic acid, HGF, Notch and IGFs. IGFs are well known to affect late stages of muscle development and to promote both proliferation and differentiation. We examined their roles in early stage limb bud myogenesis using chicken embryos as an experimental model. Grafting beads soaked in purified recombinant IGF-I, IGF-II or small molecule inhibitors of specific signaling pathways into developing chick embryo limbs showed that both IGF-I and IGF-II induce expression of the early stage myogenic markers pax3 and MyoD as well as myogenin. Their effects on pax3 and MyoD expression were blocked by inhibitors of both the IGF type I receptor (picropodophyllotoxin, PPP) and MEK (U0126). The PI3K inhibitor LY294002 blocked IGF-II, but not IGF-I, induction of pax3 mRNA as well as the IGF-I, but not IGF-II, induction of MyoD mRNA. In addition SU5402, an FGFR/ VEGFR inhibitor, blocked the induction of MyoD by both IGFs but had no effect on pax3 induction, suggesting a role for FGF or VEGF signaling in their induction of MyoD. This was confirmed by in situ hybridization showing that FGF18, a known regulator of MyoD in limb myoblasts, was induced by IGF-I. In addition to their well-known effects on later stages of myogenesis via their induction of myogenin expression, both IGF-I and IGF-II induced pax3 and MyoD expression in developing chick embryos, indicating that they also regulate early stages of myogenesis. The data suggests that the IGFs may have slightly different effects on IGF1R signal transduction via PI3K and that their stimulatory effects on MyoD expression may be indirect, possibly via induction of FGF18 expression.
[Mh] Termos MeSH primário: Embrião de Galinha/efeitos dos fármacos
Membro Posterior/efeitos dos fármacos
Fator de Crescimento Insulin-Like II/farmacologia
Fator de Crescimento Insulin-Like I/farmacologia
Desenvolvimento Muscular/efeitos dos fármacos
Músculo Esquelético/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Butadienos/farmacologia
Embrião de Galinha/metabolismo
Cromonas/farmacologia
Inibidores Enzimáticos/farmacologia
Fatores de Crescimento de Fibroblastos/genética
Fatores de Crescimento de Fibroblastos/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Membro Posterior/metabolismo
Morfolinas/farmacologia
Desenvolvimento Muscular/fisiologia
Músculo Esquelético/metabolismo
Proteína MyoD/genética
Proteína MyoD/metabolismo
Miogenina/genética
Miogenina/metabolismo
Nitrilos/farmacologia
Fator de Transcrição PAX3/genética
Fator de Transcrição PAX3/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Podofilotoxina/análogos & derivados
Podofilotoxina/farmacologia
Pirróis/farmacologia
Receptor IGF Tipo 1/antagonistas & inibidores
Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Chromones); 0 (Enzyme Inhibitors); 0 (Morpholines); 0 (MyoD Protein); 0 (Myogenin); 0 (Nitriles); 0 (PAX3 Transcription Factor); 0 (Pyrroles); 0 (SU 5402); 0 (U 0126); 0 (fibroblast growth factor 18); 0F35AOI227 (picropodophyllin); 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one); 62031-54-3 (Fibroblast Growth Factors); 67763-96-6 (Insulin-Like Growth Factor I); 67763-97-7 (Insulin-Like Growth Factor II); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, IGF Type 1); EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor); L36H50F353 (Podophyllotoxin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185775


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[PMID]:28893904
[Au] Autor:Ouyang W; Guo P; Fang H; Frucht DM
[Ad] Endereço:From the Division of Biotechnology Review and Research II, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993.
[Ti] Título:Anthrax lethal toxin rapidly reduces c-Jun levels by inhibiting c-Jun gene transcription and promoting c-Jun protein degradation.
[So] Source:J Biol Chem;292(43):17919-17927, 2017 Oct 27.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Anthrax is a life-threatening disease caused by infection with , which expresses lethal factor and the receptor-binding protective antigen. These two proteins combine to form anthrax lethal toxin (LT), whose proximal targets are mitogen-activated kinase kinases (MKKs). However, the downstream mediators of LT toxicity remain elusive. Here we report that LT exposure rapidly reduces the levels of c-Jun, a key regulator of cell proliferation and survival. Blockade of proteasome-dependent protein degradation with the 26S proteasome inhibitor MG132 largely restored c-Jun protein levels, suggesting that LT promotes degradation of c-Jun protein. Using the MKK1/2 inhibitor U0126, we further show that MKK1/2-Erk1/2 pathway inactivation similarly reduces c-Jun protein, which was also restored by MG132 pre-exposure. Interestingly, c-Jun protein rebounded to normal levels 4 h following U0126 exposure but not after LT exposure. The restoration of c-Jun in U0126-exposed cells was associated with increased c-Jun mRNA levels and was blocked by inactivation of the JNK1/2 signaling pathway. These results indicate that LT reduces c-Jun both by promoting c-Jun protein degradation via inactivation of MKK1/2-Erk1/2 signaling and by blocking c-Jun gene transcription via inactivation of MKK4-JNK1/2 signaling. In line with the known functions of c-Jun, LT also inhibited cell proliferation. Ectopic expression of LT-resistant MKK2 and MKK4 variants partially restored Erk1/2 and JNK1/2 signaling in LT-exposed cells, enabling the cells to maintain relatively normal c-Jun protein levels and cell proliferation. Taken together, these findings indicate that LT reduces c-Jun protein levels via two distinct mechanisms, thereby inhibiting critical cell functions, including cellular proliferation.
[Mh] Termos MeSH primário: Antígenos de Bactérias/farmacologia
Bacillus anthracis/química
Toxinas Bacterianas/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Proteólise/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-jun/metabolismo
Transcrição Genética/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antígenos de Bactérias/química
Toxinas Bacterianas/química
Butadienos/farmacologia
Células Hep G2
Seres Humanos
MAP Quinase Quinase 1/genética
MAP Quinase Quinase 1/metabolismo
MAP Quinase Quinase 2/genética
MAP Quinase Quinase 2/metabolismo
Sistema de Sinalização das MAP Quinases/genética
Camundongos
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Nitrilos/farmacologia
Proteínas Proto-Oncogênicas c-jun/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (Butadienes); 0 (Nitriles); 0 (Proto-Oncogene Proteins c-jun); 0 (U 0126); 0 (anthrax toxin); EC 2.7.1.- (MAP2K2 protein, human); EC 2.7.11.24 (MAPK1 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 2.7.12.2 (MAP Kinase Kinase 2); EC 2.7.12.2 (MAP2K1 protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.805648


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[PMID]:28803474
[Au] Autor:Tanaka S; Shiomi S; Ishikawa H
[Ad] Endereço:Department of Chemistry, Graduate School of Science and Technology, Kumamoto University , 2-39-1, Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
[Ti] Título:Bioinspired Indole Prenylation Reactions in Water.
[So] Source:J Nat Prod;80(8):2371-2378, 2017 Aug 25.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Isoprene units derived from dimethylallyl diphosphate (DMAPP) are an important motif in many natural products including terpenoids, carotenoids, steroids, and natural rubber. Understanding the chemical characteristics of DMAPP is an important topic in natural products chemistry, organic chemistry, and biochemistry. We have developed a direct bioinspired indole prenylation reaction using DMAPP or its equivalents as the electrophile in homogeneous aqueous acidic media in the absence of enzyme to provide prenylated indole products. After establishing the bioinspired indole prenylation reaction, this was then used to achieve the synthesis of a series of natural products, namely, N-prenylcyclo-l-tryptophyl-l-proline, tryprostatins, rhinocladins, and terezine D.
[Mh] Termos MeSH primário: Butadienos/química
Dipeptídeos/química
Hemiterpenos/química
Indóis/química
Compostos Organofosforados/química
Pentanos/química
Prolina/análogos & derivados
Prolina/química
Terpenos/química
[Mh] Termos MeSH secundário: Produtos Biológicos
Indóis/síntese química
Estrutura Molecular
Prenilação
Terpenos/síntese química
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biological Products); 0 (Butadienes); 0 (Dipeptides); 0 (Hemiterpenes); 0 (Indoles); 0 (Organophosphorus Compounds); 0 (Pentanes); 0 (Terpenes); 0 (tryptophyl-proline); 059QF0KO0R (Water); 0A62964IBU (isoprene); 358-72-5 (3,3-dimethylallyl pyrophosphate); 9DLQ4CIU6V (Proline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.7b00464



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