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[PMID]:29329317
[Au] Autor:Jeong BY; Lee HY; Park CG; Kang J; Yu SL; Choi DR; Han SY; Park MH; Cho S; Lee SY; Hwang WM; Yun SR; Ryu HM; Oh EJ; Park SH; Kim YL; Yoon SH
[Ad] Endereço:Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
[Ti] Título:Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury.
[So] Source:PLoS One;13(1):e0191034, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.
[Mh] Termos MeSH primário: Lesão Renal Aguda/metabolismo
Meios de Contraste/efeitos adversos
NADPH Oxidase 4/metabolismo
Estresse Oxidativo
[Mh] Termos MeSH secundário: Lesão Renal Aguda/induzido quimicamente
Animais
Apoptose/efeitos dos fármacos
Linhagem Celular
Ativação Enzimática
Inativação Gênica
Seres Humanos
Iohexol/farmacologia
Túbulos Renais Proximais/citologia
Túbulos Renais Proximais/efeitos dos fármacos
Túbulos Renais Proximais/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
NADPH Oxidase 4/genética
Espécies Reativas de Oxigênio/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Contrast Media); 0 (Reactive Oxygen Species); 11062-77-4 (Superoxides); 4419T9MX03 (Iohexol); EC 1.6.3.- (NADPH Oxidase 4)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191034


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[PMID]:28452222
[Au] Autor:Zhu Y; Serra A; Guo T; Park JE; Zhong Q; Sze SK
[Ad] Endereço:School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive 637551, Singapore.
[Ti] Título:Application of Nanosecond Laser Photolysis Protein Footprinting to Study EGFR Activation by EGF in Cells.
[So] Source:J Proteome Res;16(6):2282-2293, 2017 Jun 02.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mass spectrometry-based protein footprinting emerged as a useful technology to understand protein ligand interactions in vitro. We have previously demonstrated the application of footprinting in live E. coli cells. Here, we further optimized an ultrafast laser photolysis hydroxyl radical footprinting method and applied it to study the interaction of EGF and EGFR in live mammalian cells. This method used a nanosecond laser to photochemically generate a burst of hydroxyl radicals in situ in-cell suspension to oxidize the amino acids on the protein surface. Mass spectrometric analysis of the thus modified peptides was interpreted to probe the solvent-accessible surface areas of the protein in its native biological state with and without EGF activation. Our footprinting data agreed with the two relevant EGFR crystal structures, indicating that this in-cell laser photolysis footprinting technique is a valid approach to study the structural properties of integral membrane proteins directly in the native environment.
[Mh] Termos MeSH primário: Fator de Crescimento Epidérmico/metabolismo
Pegadas de Proteínas/métodos
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/química
Ativação Enzimática
Células HEK293
Seres Humanos
Radical Hidroxila
Lasers
Proteínas de Membrana/metabolismo
Estrutura Molecular
Oxirredução
Fotólise
Receptor do Fator de Crescimento Epidérmico/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Amino Acids); 0 (Membrane Proteins); 3352-57-6 (Hydroxyl Radical); 62229-50-9 (Epidermal Growth Factor); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[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:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.7b00154


  3 / 114417 MEDLINE  
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[PMID]:28455143
[Au] Autor:Li H; Li B; Larose L
[Ad] Endereço:Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
[Ti] Título:IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
[So] Source:Cell Signal;36:79-90, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Endorribonucleases/metabolismo
Proteínas Oncogênicas/deficiência
Proteínas Oncogênicas/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/química
Animais
Ativação Enzimática/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Inativação Gênica/efeitos dos fármacos
Células HeLa
Células Hep G2
Seres Humanos
Camundongos
MicroRNAs/metabolismo
Proteínas Oncogênicas/química
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
Domínios Proteicos
Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Estabilidade de RNA/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (MIRN122 microRNA, human); 0 (MicroRNAs); 0 (Nck protein); 0 (Oncogene Proteins); 0 (RNA, Messenger); 67526-95-8 (Thapsigargin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.- (Endoribonucleases); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28460458
[Au] Autor:Fang Y; Wang J; Wang G; Zhou C; Wang P; Zhao S; Zhao S; Huang S; Su W; Jiang P; Chang A; Xiang R; Sun P
[Ad] Endereço:Department of Immunology, School of Medicine, Nankai University, Tianjin, China.
[Ti] Título:Inactivation of p38 MAPK contributes to stem cell-like properties of non-small cell lung cancer.
[So] Source:Oncotarget;8(16):26702-26717, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery. In contrast, inactivation of p38 in lung cancer cells leads to upregulation of the stemness proteins, thus promoting the cancer stem cell properties of these cells. These findings have demonstrated a novel mechanism by which cancer stem cell properties are acquired and maintained in a cancer cell population, and have revealed a new function of the p38 pathway in suppressing cancer development. These studies have also identified a new pathway that can potentially serve as a target for cancer therapies aimed at eliminating CSCs.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Neoplasias Pulmonares/metabolismo
Células-Tronco Neoplásicas/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Carcinoma Pulmonar de Células não Pequenas/genética
Linhagem Celular Tumoral
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Modelos Animais de Doenças
Ativação Enzimática
Regulação Neoplásica da Expressão Gênica
Xenoenxertos
Seres Humanos
Neoplasias Pulmonares/genética
Masculino
Camundongos
Fosforilação
Complexo de Endopeptidases do Proteassoma/metabolismo
Estabilidade Proteica
Proteólise
Fatores de Transcrição SOXB1/genética
Fatores de Transcrição SOXB1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15804


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[PMID]:28460435
[Au] Autor:Li ZW; Zhu YR; Zhou XZ; Zhuo BB; Wang XD
[Ad] Endereço:The Center of Diagnosis and Treatment for Children's Bone Diseases, The Children's Hospital Affiliated to Soochow University, Suzhou, China.
[Ti] Título:microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation.
[So] Source:Oncotarget;8(16):26424-26433, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Forced-activation of AMP-activated protein kinase (AMPK) can possibly inhibit osteoblastoma cells. Here, we aim to provoke AMPK activation via microRNA silencing its phosphatase Ppm1e (protein phosphatase Mg2+/Mn2+-dependent 1e). We showed that microRNA-135b-5p ("miR-135b-5p"), the anti-Ppm1e microRNA, was significantly downregulated in human osteoblastoma tissues. It was correlated with Ppm1e upregulation and AMPKα1 de-phosphorylation. Forced-expression of miR-135b-5p in human osteoblastoma cells (MG-63 and U2OS lines) silenced Ppm1e, and induced a profound AMPKα1 phosphorylation (at Thr-172). Osteoblastoma cell proliferation was inhibited after miR-135b-5p expression. Intriguingly, Ppm1e shRNA knockdown similarly induced AMPKα1 phosphorylation, causing osteoblastoma cell proliferation. Reversely, AMPKα1 shRNA knockdown or dominant negative mutation almost abolished miR-135b-5p's actions in osteoblastoma cells. Further in vivo studies demonstrated that U2OS tumor growth in mice was dramatically inhibited after expressing miR-135b-5p or Ppm1e shRNA. Together, our results suggest that miR-135b-induced Ppm1e silence induces AMPK activation to inhibit osteoblastoma cell proliferation.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Neoplasias Ósseas/genética
Neoplasias Ósseas/metabolismo
Inativação Gênica
MicroRNAs/genética
Osteoblastoma/genética
Osteoblastoma/metabolismo
Proteína Fosfatase 2C/genética
[Mh] Termos MeSH secundário: Animais
Neoplasias Ósseas/patologia
Linhagem Celular Tumoral
Proliferação Celular
Modelos Animais de Doenças
Ativação Enzimática
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Seres Humanos
Camundongos
Mutação
Osteoblastoma/patologia
Fosforilação
RNA Interferente Pequeno/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN135 microRNA, human); 0 (MicroRNAs); 0 (RNA, Small Interfering); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 3.1.3.16 (PPM1E protein, human); EC 3.1.3.16 (Protein Phosphatase 2C)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15477


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[PMID]:29409796
[Au] Autor:Li H; Shin SE; Seo MS; An JR; Choi IW; Jung WK; Firth AL; Lee DS; Yim MJ; Choi G; Lee JM; Na SH; Park WS
[Ad] Endereço:Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea.
[Ti] Título:The anti-diabetic drug dapagliflozin induces vasodilation via activation of PKG and Kv channels.
[So] Source:Life Sci;197:46-55, 2018 Mar 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIM: Considering the clinical efficacy of dapagliflozin in patients with type 2 DM and the pathophysiological relevance of Kv channels for vascular reactivity. We investigate the vasodilatory effect of dapagliflozin and related mechanisms using phenylephrine (Phe)-induced contracted aortic rings. MATERIAL AND METHODS: Arterial tone measurement was performed in aortic smooth muscle. KEY FINDINGS: Application of dapagliflozin induced vasodilation in a concentration-dependent manner. Pre-treatment with the BK channel inhibitor paxilline, the K channel inhibitor glibenclamide, and the Kir channel inhibitor Ba did not change dapagliflozin-induced vasodilation. However, application of the Kv channels inhibitor 4-AP effectively inhibited dapagliflozin-induced vasodilation. Application of the Ca channel inhibitor nifedipine and the sarcoplasmic/endoplasmic reticulum Ca -ATPase (SERCA) pump inhibitor thapsigargin did not alter the vasodilatory effect of dapagliflozin. Moreover, the adenylyl cyclase inhibitor SQ 22536 and the protein kinase A (PKA) inhibitor KT 5720 had no effect on dapagliflozin-induced vasodilation. Although guanylyl cyclase inhibitors, NS 2028 and ODQ, did not reduce the vasodilatory effect of dapagliflozin, the protein kinase G (PKG) inhibitor KT 5823 effectively inhibited dapagliflozin-induced vasodilation. The vasodilatory effect of dapagliflozin was not affected by elimination of the endothelium. Furthermore, pretreatment with the nitric oxide synthase inhibitor L-NAME or the small-conductance Ca -activated K (SKCa) channel inhibitor apamin did not change the vasodilatory effect of dapagliflozin. SIGNIFICANCE: We concluded that dapagliflozin induced vasodilation via the activation of Kv channels and PKG, and was independent of other K channels, Ca channels, intracellular Ca , and the endothelium.
[Mh] Termos MeSH primário: Aorta/metabolismo
Compostos Benzidrílicos/farmacologia
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo
Glucosídeos/farmacologia
Hipoglicemiantes/farmacologia
Músculo Liso Vascular/metabolismo
Miócitos de Músculo Liso/metabolismo
Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo
Vasodilatação/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Aorta/fisiopatologia
Ativação Enzimática/efeitos dos fármacos
Masculino
Músculo Liso Vascular/fisiopatologia
Coelhos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol); 0 (Benzhydryl Compounds); 0 (Glucosides); 0 (Hypoglycemic Agents); 0 (Potassium Channels, Voltage-Gated); EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


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[PMID]:28461069
[Au] Autor:Shiryaev SA; Farhy C; Pinto A; Huang CT; Simonetti N; Elong Ngono A; Dewing A; Shresta S; Pinkerton AB; Cieplak P; Strongin AY; Terskikh AV
[Ad] Endereço:Sanford-Burnham-Prebys Medical Discovery Institute, Center for Neuroscience, Aging, and Stem Cell Research, La Jolla, CA 92037, United States.
[Ti] Título:Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.
[So] Source:Antiviral Res;143:218-229, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The recent re-emergence of Zika virus (ZIKV) , a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents. Like other flaviviruses, ZIKV expresses an NS2B-NS3 protease, which consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Here, we report the enzymatic characterization of ZIKV protease, and we identify structural scaffolds for allosteric small-molecule inhibitors of this protease. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrated efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. The inhibitory scaffolds could be further developed into valuable research reagents and, ultimately, provide a roadmap for the selection of efficient inhibitors of ZIKV infection.
[Mh] Termos MeSH primário: Sítio Alostérico
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/química
Zika virus/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antivirais/antagonistas & inibidores
Antivirais/química
Sequência de Bases
Ativação Enzimática
Feminino
Flavivirus/química
Expressão Gênica
Seres Humanos
Concentração Inibidora 50
Camundongos
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Fatores de Transcrição SOXB1/genética
Alinhamento de Sequência
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Células-Tronco
Proteínas não Estruturais Virais/efeitos dos fármacos
Proteínas Virais/química
Proteínas Virais/genética
Zika virus/química
Zika virus/genética
Zika virus/crescimento & desenvolvimento
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (NS2B protein, flavivirus); 0 (NS3 protein, flavivirus); 0 (Protease Inhibitors); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); 0 (Viral Nonstructural Proteins); 0 (Viral Proteins); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29338043
[Au] Autor:Almeida VM; Frutuoso MA; Marana SR
[Ad] Endereço:Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
[Ti] Título:Search for independent (ß/α)4 subdomains in a (ß/α)8 barrel ß-glucosidase.
[So] Source:PLoS One;13(1):e0191282, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteins that fold as (ß/α)8 barrels are thought to have evolved from half-barrels that underwent duplication and fusion events. The evidence is particularly clear for small barrels, which have almost identical halves. Additionally, computational calculations of the thermodynamic stability of these structures in the presence of denaturants have revealed that (ß/α)8 barrels contain two subunits or domains corresponding to half-barrels. Hence, within (ß/α)8 barrels, half-barrels are self-contained units. Here, we tested this hypothesis using ß-glucosidase from the bacterium Thermotoga maritima (bglTm), which has a (ß/α)8 barrel structure. Mutations were introduced to disrupt the noncovalent contacts between its halves and reveal the presence of two domains within bglTm, thus resulting in the creation of mutants T1 (containing W12A and I217A mutations) and T2 (containing W12A, H195A, I217A and F404A mutations). Mutants T1 and T2 were properly folded, as indicated by their fluorescence spectra and enzyme kinetic parameters. T1 and wild-type bglTm were equally stable, as shown by the results of thermal inactivation, differential scanning fluorimetry and guanidine hydrochloride denaturation experiments. However, T2 showed a first-order inactivation at 80°C, a single melting temperature of 82°C and only one transition concentration (c50) in 2.4 M guanidine hydrochloride. Additionally, T1 and T2 exhibited a cooperative denaturation process that followed a two-state model (m-values equal to 1.4 and 1.6 kcal/mol/M, respectively), similar to that of wild-type bglTm (1.2 kcal/mol/M). Hence, T1 and T2 each denatured as a single unit, although they contained different degrees of disruption between their halves. In conclusion, bglTm halves are equivalent in terms of their thermal and chemical stability; thus, their separate contributions to (ß/α)8 barrel unfolding cannot be disentangled.
[Mh] Termos MeSH primário: beta-Glucosidase/química
beta-Glucosidase/metabolismo
[Mh] Termos MeSH secundário: Ativação Enzimática
Cinética
Modelos Moleculares
Mutação
Conformação Proteica em Folha beta
Domínios Proteicos
Temperatura Ambiente
Thermotoga maritima/enzimologia
beta-Glucosidase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.2.1.21 (beta-Glucosidase)
[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:10.1371/journal.pone.0191282


  9 / 114417 MEDLINE  
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[PMID]:29324830
[Au] Autor:Skeate JG; Da Silva DM; Chavez-Juan E; Anand S; Nuccitelli R; Kast WM
[Ad] Endereço:Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA, United States of America.
[Ti] Título:Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.
[So] Source:PLoS One;13(1):e0191311, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s) associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.
[Mh] Termos MeSH primário: Imunidade Adaptativa
Morte Celular/imunologia
Transformação Celular Viral
Estimulação Elétrica
Papillomavirus Humano 16/fisiologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD8/metabolismo
Caspase 3/metabolismo
Caspase 7/metabolismo
Linhagem Celular Tumoral
Ativação Enzimática
Seres Humanos
Camundongos
Nanotecnologia
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CD8 Antigens); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 7)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191311


  10 / 114417 MEDLINE  
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[PMID]:28471109
[Au] Autor:Ye SF; Yang Y; Wu L; Ma WW; Zeng HH
[Ad] Endereço:State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
[Ti] Título:Ethaselen: a novel organoselenium anticancer agent targeting thioredoxin reductase 1 reverses cisplatin resistance in drug-resistant K562 cells by inducing apoptosis.
[So] Source:J Zhejiang Univ Sci B;18(5):373-382, 2017 May.
[Is] ISSN:1862-1783
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase (TrxR) activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin (CDDP) cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and combination index (CI), showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species (ROS) generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores (PTPs). In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB (NF-κB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem
Cisplatino/administração & dosagem
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Compostos Organosselênicos/administração & dosagem
Tiorredoxina Redutase 1/antagonistas & inibidores
Tiorredoxina Redutase 1/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem
Proliferação Celular/efeitos dos fármacos
Tamanho Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ativação Enzimática/efeitos dos fármacos
Seres Humanos
Células K562
Terapia de Alvo Molecular/métodos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane); 0 (Antineoplastic Agents); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Organoselenium Compounds); EC 1.8.1.9 (TXNRD1 protein, human); EC 1.8.1.9 (Thioredoxin Reductase 1); Q20Q21Q62J (Cisplatin)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.1631/jzus.B1600073



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