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  1 / 113414 MEDLINE  
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[PMID]:29381770
[Au] Autor:Lin CY; Lin LY
[Ad] Endereço:Institute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
[Ti] Título:The conserved basic residues and the charged amino acid residues at the α-helix of the zinc finger motif regulate the nuclear transport activity of triple C2H2 zinc finger proteins.
[So] Source:PLoS One;13(1):e0191971, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Zinc finger (ZF) motifs on proteins are frequently recognized as a structure for DNA binding. Accumulated reports indicate that ZF motifs contain nuclear localization signal (NLS) to facilitate the transport of ZF proteins into nucleus. We investigated the critical factors that facilitate the nuclear transport of triple C2H2 ZF proteins. Three conserved basic residues (hot spots) were identified among the ZF sequences of triple C2H2 ZF proteins that reportedly have NLS function. Additional basic residues can be found on the α-helix of the ZFs. Using the ZF domain (ZFD) of Egr-1 as a template, various mutants were constructed and expressed in cells. The nuclear transport activity of various mutants was estimated by analyzing the proportion of protein localized in the nucleus. Mutation at any hot spot of the Egr-1 ZFs reduced the nuclear transport activity. Changes of the basic residues at the α-helical region of the second ZF (ZF2) of the Egr-1 ZFD abolished the NLS activity. However, this activity can be restored by substituting the acidic residues at the homologous positions of ZF1 or ZF3 with basic residues. The restored activity dropped again when the hot spots at ZF1 or the basic residues in the α-helix of ZF3 were mutated. The variations in nuclear transport activity are linked directly to the binding activity of the ZF proteins with importins. This study was extended to other triple C2H2 ZF proteins. SP1 and KLF families, similar to Egr-1, have charged amino acid residues at the second (α2) and the third (α3) positions of the α-helix. Replacing the amino acids at α2 and α3 with acidic residues reduced the NLS activity of the SP1 and KLF6 ZFD. The reduced activity can be restored by substituting the α3 with histidine at any SP1 and KLF6 ZFD. The results show again the interchangeable role of ZFs and charge residues in the α-helix in regulating the NLS activity of triple C2H2 ZF proteins.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Núcleo Celular/metabolismo
Dedos de Zinco
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191971


  2 / 113414 MEDLINE  
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Ugrinowitsch, Carlos
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[PMID]:29324825
[Au] Autor:Damas F; Libardi CA; Ugrinowitsch C; Vechin FC; Lixandrão ME; Snijders T; Nederveen JP; Bacurau AV; Brum P; Tricoli V; Roschel H; Parise G; Phillips SM
[Ad] Endereço:School of Physical Education and Sport, University of São Paulo, São Paulo, São Paulo, Brazil.
[Ti] Título:Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men.
[So] Source:PLoS One;13(1):e0191039, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased 48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns], ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]). Increased SC content was not coupled with changes in myonuclear number. SC have a more pronounced role in muscle repair during the initial phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Proteínas Musculares/metabolismo
Células Satélites de Músculo Esquelético/fisiologia
Levantamento de Peso
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Masculino
Células Satélites de Músculo Esquelético/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Muscle Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191039


  3 / 113414 MEDLINE  
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[PMID]:29214531
[Au] Autor:Zhang J; Liang L; Guan X; Deng R; Qu H; Huang D; Xu S; Liang C; Xu W
[Ad] Endereço:State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun, Jilin, 130012, China.
[Ti] Título:In situ, accurate, surface-enhanced Raman scattering detection of cancer cell nucleus with synchronous location by an alkyne-labeled biomolecular probe.
[So] Source:Anal Bioanal Chem;410(2):585-594, 2018 Jan.
[Is] ISSN:1618-2650
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A surface-enhanced Raman scattering (SERS) method for in situ detection and analysis of the intranuclear biomolecular information of a cell has been developed based on a small, biocompatible, nuclear-targeting alkyne-tagged deoxyribonucleic acid (DNA) probe (5-ethynyl-2'-deoxyuridine, EDU) that can specially accumulate in the cell nucleus during DNA replications to precisely locate the nuclear region without disturbance in cell biological activities and functions. Since the specific alkyne group shows a Raman peak in the Raman-silent region of cells, it is an interior label to visualize the nuclear location synchronously in real time when measuring the SERS spectra of a cell. Because no fluorescent-labeled dyes were used for locating cell nuclei, this method is simple, nondestructive, non- photobleaching, and valuable for the in situ exploration of vital physiological processes with DNA participation in cell organelles. Graphical abstract A universal strategy was developed to accurately locate the nuclear region and obtain precise molecular information of cell nuclei by SERS.
[Mh] Termos MeSH primário: Alquinos/análise
Núcleo Celular/patologia
Desoxiuridina/análogos & derivados
Neoplasias/patologia
[Mh] Termos MeSH secundário: Núcleo Celular/química
Desoxiuridina/análise
Seres Humanos
Células MCF-7
Microscopia de Fluorescência/métodos
Neoplasias/química
Imagem Óptica/métodos
Análise Espectral Raman/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkynes); G373S00W2J (5-ethynyl-2'-deoxyuridine); W78I7AY22C (Deoxyuridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1007/s00216-017-0761-4


  4 / 113414 MEDLINE  
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[PMID]:29031765
[Au] Autor:Boakye YD; Groyer L; Heiss EH
[Ad] Endereço:Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
[Ti] Título:An increased autophagic flux contributes to the anti-inflammatory potential of urolithin A in macrophages.
[So] Source:Biochim Biophys Acta;1862(1):61-70, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An extract of Phyllanthus muellerianus and its constituent geraniin have been reported to exert anti-inflammatory activity in vivo. However, orally consumed geraniin, an ellagitannin, shows low bioavailability and undergoes metabolization to urolithins by gut microbiota. This study aimed at comparing geraniin and urolithin A with respect to inhibition of M1 (LPS) polarization of murine J774.1 macrophages and shedding more light on possible underlying mechanisms. METHODS: Photometric, fluorimetric as well as luminescence-based assays monitored production of reactive oxygen species (ROS) and nitric oxide (NO), cell viability or reporter gene expression. Western blot analyses and confocal microscopy showed abundance and localization of target proteins, respectively. RESULTS: Urolithin A is a stronger inhibitor of M1 (LPS) macrophage polarization (production of NO, ROS and pro-inflammatory proteins) than geraniin. Urolithin A leads to an elevated autophagic flux in macrophages. Inhibition of autophagy in M1 (LPS) macrophages overcomes the suppressed nuclear translocation of p65 (NF-kB; nuclear factor kB), the reduced expression of pro-inflammatory genes as well as the diminished NO production brought about by urolithin A. The increased autophagic flux is furthermore associated with impaired Akt/mTOR (mammalian target of rapamycin) signaling in urolithin A-treated macrophages. CONCLUSIONS AND GENERAL SIGNIFICANCE: Intestinal metabolization may boost the potential health benefit of widely consumed dietary ellagitannins, as suggested by side by side comparison of geraniin and urolithin A in M1(LPS) macrophages. Increased activity of the autophagic cellular recycling machinery aids the anti-inflammatory bioactivity of urolithin A.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Autofagia/efeitos dos fármacos
Cumarínicos/farmacologia
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Animais
Células CHO
Núcleo Celular/metabolismo
Cricetinae
Cricetulus
Células HEK293
Seres Humanos
Lipopolissacarídeos/toxicidade
Camundongos
Óxido Nítrico/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fator de Transcrição RelA/metabolismo
Proteínas ral de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Coumarins); 0 (Lipopolysaccharides); 0 (RELA protein, human); 0 (Reactive Oxygen Species); 0 (Transcription Factor RelA); 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one); 31C4KY9ESH (Nitric Oxide); EC 3.6.1.- (Rala protein, mouse); EC 3.6.5.2 (ral GTP-Binding Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


  5 / 113414 MEDLINE  
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[PMID]:28457165
[Au] Autor:de Simone A; Hubbard R; de la Torre NV; Velappan Y; Wilson M; Considine MJ; Soppe WJJ; Foyer CH
[Ad] Endereço:1 Centre for Plant Sciences, Faculty of Biological Sciences, University of Leeds , Leeds, United Kingdom .
[Ti] Título:Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.
[So] Source:Antioxid Redox Signal;27(18):1505-1519, 2017 Dec 20.
[Is] ISSN:1557-7716
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. RESULTS: Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. INNOVATION: These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. CONCLUSIONS: Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 27, 1505-1519.
[Mh] Termos MeSH primário: Arabidopsis/crescimento & desenvolvimento
Meristema/embriologia
Oxirredução
Proteínas de Plantas/genética
[Mh] Termos MeSH secundário: Arabidopsis/embriologia
Arabidopsis/genética
Ciclo Celular
Núcleo Celular/genética
Núcleo Celular/metabolismo
Citosol/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Regulação da Expressão Gênica de Plantas
Germinação
Meristema/genética
Raízes de Plantas/embriologia
Raízes de Plantas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2016.6959


  6 / 113414 MEDLINE  
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[PMID]:28456783
[Au] Autor:Cai S; Li Y; Bai JY; Zhang ZQ; Wang Y; Qiao YB; Zhou XZ; Yang B; Tian Y; Cao C
[Ad] Endereço:Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
[Ti] Título:Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.
[So] Source:Oncotarget;8(21):35061-35068, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have previously shown that Gαi3 is elevated in human glioma, mediating Akt activation and cancer cell proliferation. Here, we imply that Gαi3 could also be important for irradiation resistance. In A172 human glioma cells, Gαi3 knockdown (by targeted shRNAs) or dominant-negative mutation significantly potentiated irradiation-induced cell apoptosis. Reversely, forced over-expression of wild-type or constitutively-active Gαi3 inhibited irradiation-induced A172 cell apoptosis. Irradiation in A172 cells induced Gαi3 translocation to cell nuclei and association with local protein DNA-dependent protein kinase (DNA-PK) catalytic subunit. This association was important for DNA damage repair. Gαi3 knockdown, depletion (using Gαi3 knockout MEFs) or dominant-negative mutation potentiated irradiation-induced DNA damages. On the other hand, expression of the constitutively-active Gαi3 in A172 cells inhibited DNA damage by irradiation. Together, these results indicate a novel function of Gαi3 in irradiation-resistance in human glioma cells.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/metabolismo
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo
Glioma/metabolismo
Tolerância a Radiação
[Mh] Termos MeSH secundário: Neoplasias Encefálicas/genética
Neoplasias Encefálicas/radioterapia
Linhagem Celular Tumoral
Núcleo Celular/metabolismo
Dano ao DNA
Proteína Quinase Ativada por DNA/metabolismo
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Glioma/genética
Glioma/radioterapia
Seres Humanos
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 3.6.5.1 (GNAI3 protein, human); EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17043


  7 / 113414 MEDLINE  
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[PMID]:28456662
[Au] Autor:Kinkar L; Laurimäe T; Sharbatkhori M; Mirhendi H; Kia EB; Ponce-Gordo F; Andresiuk V; Simsek S; Lavikainen A; Irshadullah M; Umhang G; Oudni-M'rad M; Acosta-Jamett G; Rehbein S; Saarma U
[Ad] Endereço:Department of Zoology, Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise 46, 50410 Tartu, Estonia.
[Ti] Título:New mitogenome and nuclear evidence on the phylogeny and taxonomy of the highly zoonotic tapeworm Echinococcus granulosus sensu stricto.
[So] Source:Infect Genet Evol;52:52-58, 2017 Aug.
[Is] ISSN:1567-7257
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cystic echinococcosis, a zoonotic disease caused by Echinococcus granulosus sensu lato (s. l.), is a significant global public health concern. Echinococcus granulosus s. l. is currently divided into numerous genotypes (G1-G8 and G10) of which G1-G3 are the most frequently implicated genotypes in human infections. Although it has been suggested that G1-G3 could be regarded as a distinct species E. granulosus sensu stricto (s. s.), the evidence to support this is inconclusive. Most importantly, data from nuclear DNA that provide means to investigate the exchange of genetic material between G1-G3 is lacking as none of the published nuclear DNA studies have explicitly included G2 or G3. Moreover, the commonly used relatively short mtDNA sequences, including the complete cox1 gene, have not allowed unequivocal differentiation of genotypes G1-G3. Therefore, significantly longer mtDNA sequences are required to distinguish these genotypes with confidence. The main aim of this study was to evaluate the phylogenetic relations and taxonomy of genotypes G1-G3 using sequences of nearly complete mitogenomes (11,443bp) and three nuclear loci (2984bp). A total of 23 G1-G3 samples were analysed, originating from 5 intermediate host species in 10 countries. The mtDNA data demonstrate that genotypes G1 and G3 are distinct mitochondrial genotypes (separated by 37 mutations), whereas G2 is not a separate genotype or even a monophyletic cluster, but belongs to G3. Nuclear data revealed no genetic separation of G1 and G3, suggesting that these genotypes form a single species due to ongoing gene flow. We conclude that: (a) in the taxonomic sense, genotypes G1 and G3 can be treated as a single species E. granulosus s. s.; (b) genotypes G1 and G3 should be regarded as distinct genotypes only in the context of mitochondrial data; (c) we recommend excluding G2 from the genotype list.
[Mh] Termos MeSH primário: Núcleo Celular/genética
DNA de Helmintos/genética
Echinococcus granulosus/classificação
Mitocôndrias/genética
[Mh] Termos MeSH secundário: África do Norte
Animais
Ásia
Echinococcus granulosus/genética
Echinococcus granulosus/isolamento & purificação
Echinococcus granulosus/metabolismo
Europa (Continente)
Genoma Mitocondrial
Genótipo
Seres Humanos
Filogenia
Filogeografia
América do Sul
Zoonoses/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Helminth)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  8 / 113414 MEDLINE  
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[PMID]:29441916
[Au] Autor:Fan X; Wang P; Sun Y; Jiang J; Du H; Wang Z; Duan Z; Lei H; Li H
[Ti] Título:Oleanolic acid derivatives inhibit the Wnt/ß-catenin signaling pathway by promoting the phosphorylation of ß-catenin in human SMMC-7721 cells.
[So] Source:Pharmazie;71(7):398-401, 2016 Jul 07.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Oleanolic acid, isolated from privet, has shown antitumor effects in several cancers. However, the underlying molecular mechanism associated with these effects is largely unknown. In this study, we explored the effect of oleanolic acid derivatives on the Wnt/ß-catenin signaling pathway in human hepatocellular carcinoma SMMC-7721 cells. The mRNA and protein levels of related genes were determined by real-time quantitative PCR and Western blot, respectively. Treatment of SMMC-7721 cells with oleanolic acid derivatives led to the downregulation of the mRNA and protein levels of ß-catenin, c-myc, and cyclin D1. Treatment with oleanolic acid derivatives decreased the levels of ß-catenin in both the cytoplasm and the nucleus. Moreover, oleanolic acid derivatives promoted the phosphorylation of ß-catenin (Ser33/37/Thr41) in the cytoplasm. Our results suggest that oleanolic acid derivatives inhibit the Wnt/ß-catenin signaling pathway by stimulating the phosphorylation of ß-catenin (Ser33/37/Thr41) in human SMMC-7721 cells.
[Mh] Termos MeSH primário: Ácido Oleanólico/análogos & derivados
Ácido Oleanólico/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
beta Catenina/efeitos dos fármacos
beta Catenina/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Núcleo Celular/efeitos dos fármacos
Núcleo Celular/metabolismo
Ciclina D1/antagonistas & inibidores
Ciclina D1/biossíntese
Citoplasma/efeitos dos fármacos
Citoplasma/metabolismo
Regulação para Baixo/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-myc/biossíntese
RNA Mensageiro/biossíntese
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CTNNB1 protein, human); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Messenger); 0 (beta Catenin); 136601-57-5 (Cyclin D1); 6SMK8R7TGJ (Oleanolic Acid)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6536


  9 / 113414 MEDLINE  
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[PMID]:29362359
[Au] Autor:Naumann M; Pal A; Goswami A; Lojewski X; Japtok J; Vehlow A; Naujock M; Günther R; Jin M; Stanslowsky N; Reinhardt P; Sterneckert J; Frickenhaus M; Pan-Montojo F; Storkebaum E; Poser I; Freischmidt A; Weishaupt JH; Holzmann K; Troost D; Ludolph AC; Boeckers TM; Liebau S; Petri S; Cordes N; Hyman AA; Wegner F; Grill SW; Weis J; Storch A; Hermann A
[Ad] Endereço:Department of Neurology, Technische Universität Dresden, 01307, Dresden, Germany.
[Ti] Título:Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation.
[So] Source:Nat Commun;9(1):335, 2018 01 23.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease. Cytoplasmic fused in sarcoma (FUS) aggregates are pathological hallmarks of FUS-ALS. Proper shuttling between the nucleus and cytoplasm is essential for physiological cell function. However, the initial event in the pathophysiology of FUS-ALS remains enigmatic. Using human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs), we show that impairment of poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response (DDR) signaling due to mutations in the FUS nuclear localization sequence (NLS) induces additional cytoplasmic FUS mislocalization which in turn results in neurodegeneration and FUS aggregate formation. Our work suggests that a key pathophysiologic event in ALS is upstream of aggregate formation. Targeting DDR signaling could lead to novel therapeutic routes for ameliorating ALS.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/metabolismo
Dano ao DNA
Neurônios Motores/metabolismo
Mutação
Agregação Patológica de Proteínas/metabolismo
Proteína FUS de Ligação a RNA/metabolismo
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/genética
Idoso
Idoso de 80 Anos ou mais
Esclerose Amiotrófica Lateral/genética
Esclerose Amiotrófica Lateral/patologia
Diferenciação Celular
Núcleo Celular/metabolismo
Citoplasma/metabolismo
Feminino
Expressão Gênica
Seres Humanos
Células-Tronco Pluripotentes Induzidas/metabolismo
Células-Tronco Pluripotentes Induzidas/patologia
Masculino
Meia-Idade
Neurônios Motores/patologia
Sinais de Localização Nuclear/genética
Sinais de Localização Nuclear/metabolismo
Poli(ADP-Ribose) Polimerase-1/genética
Poli(ADP-Ribose) Polimerase-1/metabolismo
Agregação Patológica de Proteínas/genética
Agregação Patológica de Proteínas/patologia
Proteína FUS de Ligação a RNA/genética
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nuclear Localization Signals); 0 (RNA-Binding Protein FUS); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02299-1


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[PMID]:29444034
[Au] Autor:Liu X; Wong TTW; Shi J; Ma J; Yang Q; Wang LV
[Ti] Título:Label-free cell nuclear imaging by Grüneisen relaxation photoacoustic microscopy.
[So] Source:Opt Lett;43(4):947-950, 2018 Feb 15.
[Is] ISSN:1539-4794
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Photoacoustic microscopy (PAM) with ultraviolet (UV) laser illumination has recently been demonstrated as a promising tool that provides fast, label-free, and multilayered histologic imaging of human breast tissue. Thus far, the axial resolution has been determined ultrasonically. To enable optically defined axial resolution, we exploit the Grüneisen relaxation (GR) effect. By imaging mouse brain slices, we show that GRUV-PAM reveals detailed information about three-dimensional cell nuclear distributions and internal structures, which are important diagnostic features for cancers. Due to the nonlinear effect, GRUV-PAM also provides better contrast in images of cell nuclei.
[Mh] Termos MeSH primário: Núcleo Celular/metabolismo
Microscopia Acústica/métodos
Técnicas Fotoacústicas/métodos
[Mh] Termos MeSH secundário: Animais
Encéfalo/citologia
Encéfalo/diagnóstico por imagem
Camundongos
Microscopia Acústica/instrumentação
Técnicas Fotoacústicas/instrumentação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1364/OL.43.000947



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