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[PMID]:29351565
[Au] Autor:Peek J; Harvey C; Gray D; Rosenberg D; Kolla L; Levy-Myers R; Yin R; McMurry JL; Kerscher O
[Ad] Endereço:Biology Department, The College of William & Mary, Williamsburg, Virginia, United States of America.
[Ti] Título:SUMO targeting of a stress-tolerant Ulp1 SUMO protease.
[So] Source:PLoS One;13(1):e0191391, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1. We find that the catalytic UD domains of both ScUlp1 and KmUlp1 show a high degree of sequence conservation, complement a ulp1Δ mutant in vivo, and process a SUMO precursor in vitro. Next, to compare the SUMO-trapping features of both SUMO proteases we produced catalytically inactive recombinant fragments of the UD domains of ScUlp1 and KmUlp1, termed ScUTAG and KmUTAG respectively. Both ScUTAG and KmUTAG were able to efficiently bind a variety of purified SUMO isoforms and bound immobilized SUMO1 with nanomolar affinity. However, KmUTAG showed a greatly enhanced ability to bind SUMO and SUMO-modified proteins in the presence of oxidative, temperature and other stressors that induce protein misfolding. We also investigated whether a SUMO-interacting motif (SIM) in the UD domain of KmULP1 that is not conserved in ScUlp1 may contribute to the SUMO-binding properties of KmUTAG. In summary, our data reveal important details about how SUMO proteases target and bind their sumoylated substrates, especially under stress conditions. We also show that the robust pan-SUMO binding features of KmUTAG can be exploited to detect and study SUMO-modified proteins in cell culture systems.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/metabolismo
Proteínas Fúngicas/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Domínio Catalítico/genética
Sequência Conservada
Cisteína Endopeptidases/química
Cisteína Endopeptidases/genética
Proteínas Fúngicas/química
Proteínas Fúngicas/genética
Teste de Complementação Genética
Kluyveromyces/genética
Kluyveromyces/metabolismo
Modelos Moleculares
Proteínas Mutantes/química
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/química
Proteínas de Saccharomyces cerevisiae/genética
Homologia de Sequência de Aminoácidos
Estresse Fisiológico
Sumoilação
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Mutant Proteins); 0 (Saccharomyces cerevisiae Proteins); 0 (Small Ubiquitin-Related Modifier Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (Ulp1 protease)
[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:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191391


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[PMID]:29329335
[Au] Autor:Kyrklund M; Kummu O; Kankaanpää J; Akhi R; Nissinen A; Turunen SP; Pussinen P; Wang C; Hörkkö S
[Ad] Endereço:Medical Microbiology and Immunology, Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
[Ti] Título:Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein.
[So] Source:PLoS One;13(1):e0191216, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL) and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS), and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis.
[Mh] Termos MeSH primário: Adesinas Bacterianas/imunologia
Anticorpos Antibacterianos/biossíntese
Proteínas de Bactérias/imunologia
Cisteína Endopeptidases/imunologia
Imunoglobulina M/biossíntese
Lipoproteínas LDL/imunologia
Porphyromonas gingivalis/imunologia
[Mh] Termos MeSH secundário: Acetaldeído/análogos & derivados
Adesinas Bacterianas/química
Animais
Anticorpos Antibacterianos/metabolismo
Aterosclerose/etiologia
Aterosclerose/imunologia
Aterosclerose/prevenção & controle
Proteínas de Bactérias/química
Infecções por Bacteroidaceae/complicações
Infecções por Bacteroidaceae/imunologia
Infecções por Bacteroidaceae/microbiologia
Reações Cruzadas
Cisteína Endopeptidases/química
Modelos Animais de Doenças
Feminino
Seres Humanos
Imunização
Imunoglobulina M/metabolismo
Lectinas/química
Lectinas/imunologia
Lipoproteínas LDL/química
Malondialdeído/análogos & derivados
Malondialdeído/imunologia
Camundongos
Camundongos Knockout
Periodontite/complicações
Periodontite/imunologia
Periodontite/microbiologia
Domínios Proteicos
Receptores de LDL/deficiência
Receptores de LDL/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Antibodies, Bacterial); 0 (Bacterial Proteins); 0 (Immunoglobulin M); 0 (Lectins); 0 (Lipoproteins, LDL); 0 (Receptors, LDL); 0 (hemagglutinin A, Porphyromonas gingivalis); 0 (malondialdehyde-low density lipoprotein, mouse); 4Y8F71G49Q (Malondialdehyde); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.37 (argingipain, Porphyromonas gingivalis); GO1N1ZPR3B (Acetaldehyde)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191216


  3 / 15176 MEDLINE  
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[PMID]:28470603
[Au] Autor:Besir H
[Ad] Endereço:Protein Expression and Purification Core Facility, EMBL Heidelberg, Meyerhofstraße 1, Heidelberg, 69117, Germany. besir@embl.de.
[Ti] Título:A Generic Protocol for Purifying Disulfide-Bonded Domains and Random Protein Fragments Using Fusion Proteins with SUMO3 and Cleavage by SenP2 Protease.
[So] Source:Methods Mol Biol;1586:141-154, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recombinant expression of heterologous proteins in E. coli is well established for a wide range of proteins, although in many cases, purifying soluble and properly folded proteins remains challenging (Sorensen and Mortensen, J Biotechnol 115:113-128, 2005; Correa and Oppezzo, Methods Mol Biol 1258:27-44, 2015). Proteins that contain disulfide bonds (e.g., cytokines, growth factors) are often particularly difficult to purify in soluble form and still need optimizing of protocols in almost every step of the process (Berkmen, Protein Expr Purif 82:240-251, 2012; de Marco, Microb Cell Fact 11:129, 2012). Expression of disulfide bonded proteins in the periplasm of E. coli is one approach that can help to obtain soluble protein with the correct disulfide bridges forming in the periplasm. This offers the appropriate conditions for disulfide formation although periplasmic expression can also result in low expression levels and incorrect folding of the target protein (Schlapschy and Skerra, Methods Mol Biol 705:211-224, 2011). Generation of specific antibodies often requires a specific antigenic sequence of a protein in order to get an efficient immune response and minimize cross-reactivity of antibodies. Larger proteins like GST (Glutathione-S-transferase) or MBP (maltose binding protein) as solubilizing fusion partners are frequently used to keep antigens soluble and immunize animals. This approach has the disadvantage that the immune response against the fusion partner leads to additional antibodies that need to be separated from the antigen-specific antibodies. For both classes of proteins mentioned above, a protocol has been developed and optimized using the human version of small ubiquitin-like modifier 3 (SUMO3) protein and its corresponding protease SenP2. This chapter describes the experimental steps for expression, purification, refolding, and cleavage that are applicable to both disulfide-bonded proteins with a defined structure and random protein fragments for antibody generation or larger peptides with defined sequence that are difficult express on their own.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/genética
Dissulfetos/química
Escherichia coli/genética
Ubiquitinas/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Clonagem Molecular/métodos
Cisteína Endopeptidases/química
Cisteína Endopeptidases/metabolismo
Dissulfetos/metabolismo
Escherichia coli/metabolismo
Seres Humanos
Domínios Proteicos
Redobramento de Proteína
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Solubilidade
Ubiquitinas/química
Ubiquitinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disulfides); 0 (Recombinant Fusion Proteins); 0 (SUMO3 protein, human); 0 (Ubiquitins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (SENP2 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6887-9_9


  4 / 15176 MEDLINE  
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[PMID]:28466019
[Au] Autor:Almeida-Reis R; Theodoro-Junior OA; Oliveira BTM; Oliva LV; Toledo-Arruda AC; Bonturi CR; Brito MV; Lopes FDTQS; Prado CM; Florencio AC; Martins MA; Owen CA; Leick EA; Oliva MLV; Tibério IFLC
[Ad] Endereço:Department of Medicine, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
[Ti] Título:Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice.
[So] Source:Biomed Res Int;2017:8287125, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteinases play a key role in emphysema. inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. / mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF -, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 , collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF -positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/administração & dosagem
Proteínas de Plantas/administração & dosagem
Pneumonia/tratamento farmacológico
Enfisema Pulmonar/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Líquido da Lavagem Broncoalveolar
Seres Humanos
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Pulmão/patologia
Camundongos
Estresse Oxidativo/efeitos dos fármacos
Elastase Pancreática/toxicidade
Pneumonia/induzido quimicamente
Pneumonia/patologia
Enfisema Pulmonar/induzido quimicamente
Enfisema Pulmonar/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BbCI protein, Bauhinia bauhinoides); 0 (Plant Proteins); EC 3.4.21.36 (Pancreatic Elastase); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (cruzipain)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1155/2017/8287125


  5 / 15176 MEDLINE  
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[PMID]:27770746
[Au] Autor:Poongavanam V; Kongsted J
[Ad] Endereço:Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark.
[Ti] Título:Binding affinity models for Falcipain inhibition based on the Linear Interaction Energy method.
[So] Source:J Mol Graph Model;70:236-245, 2016 11.
[Is] ISSN:1873-4243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The high rate of drug resistance as well as the complex biochemical process of the parasite reproduction cycle makes development of new drugs for malaria a very important but challenging task. Falcipain 2 (FL2) and Falcipain 3 (FL3) are the major cysteine protease enzymes that play a central role in providing essential amino acids for the parasite's protein biosynthesis through the hemoglobin hydrolysis process. Selective inhibition of these enzymes is considered as a promising chemotherapeutic target. In the present investigation, the highly efficient linear interaction energy (LIE) method has been parameterized for binding affinity predictions and assessed with a set of 244 compounds for FL2 and FL3 inhibition. The results revealed that the van der Waals energy is very important for ligands binding to Falcipain proteins and that, overall, the electrostatic energy contribution is minor. The best models obtained for FL2 and FL3 give root mean square errors (RMSE) of 1.82 and 1.33kcal/mol respectively, for the test set. In this study, we also investigate how the choice of initial protein-ligand confirmation (pose) impacts the overall quality of the LIE models. Moreover, the transferability of LIE parameters is further discussed.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/química
Cisteína Endopeptidases/farmacologia
Transferência Linear de Energia
Modelos Moleculares
[Mh] Termos MeSH secundário: Ligantes
Simulação de Acoplamento Molecular
Análise Multivariada
Análise de Componente Principal
Pirimidinas/química
Reprodutibilidade dos Testes
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ligands); 0 (Pyrimidines); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (falcipain); EC 3.4.22.- (falcipain 2); EC 3.4.22.- (falcipain 3)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  6 / 15176 MEDLINE  
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[PMID]:27771373
[Au] Autor:Kiuchi S; Tomaru U; Ishizu A; Imagawa M; Kiuchi T; Iwasaki S; Suzuki A; Otsuka N; Deguchi T; Shimizu T; Marukawa K; Matsuno Y; Kasahara M
[Ad] Endereço:Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
[Ti] Título:Expression of cathepsins V and S in thymic epithelial tumors.
[So] Source:Hum Pathol;60:66-74, 2017 02.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cathepsins are a group of proteolytic enzymes of the endosomal/lysosomal pathway involved in the thymic development of T cells restricted by major histocompatibility complex class II molecules. In the normal thymus, cathepsin V (CTV) and cathepsin S (CTS) are expressed in cortical and medullary epithelial cells, respectively. To investigate whether cathepsins could serve as a diagnostic marker, we performed immunohistochemical analysis for CTV and CTS in 77 cases of thymic epithelial tumors. Almost all cases (59/60) of thymoma expressed CTV, whereas 28 of 60 cases of thymoma expressed CTS. Notably, CTS was expressed in most cases of type A and type AB thymomas, but not in type B thymoma. The expression of cathepsins in type AB thymoma showed a clear correlation with histologic features; CTV was found predominantly in the type B component, and CTS was frequently expressed in the type A component. In thymic carcinoma, CTV was expressed in less than half cases (7/17), and the ratio of CTS-positive cases was equivalent to that of thymoma (8/17). Cases of CTV-negative thymic carcinoma tended to have a higher incidence of recurrence than did CTV-positive cases. Although further studies with a larger number of cases are required to confirm the utility of cathepsin immunostaining, CTV and CTS appear to serve as auxiliary diagnostic and/or prognostic markers in thymic epithelial tumors.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Catepsinas/análise
Cisteína Endopeptidases/análise
Neoplasias Epiteliais e Glandulares/enzimologia
Timoma/enzimologia
Neoplasias do Timo/enzimologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Biópsia
Diagnóstico Diferencial
Feminino
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Estadiamento de Neoplasias
Neoplasias Epiteliais e Glandulares/patologia
Neoplasias Epiteliais e Glandulares/cirurgia
Valor Preditivo dos Testes
Timoma/patologia
Timoma/cirurgia
Neoplasias do Timo/patologia
Neoplasias do Timo/cirurgia
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 3.4.- (Cathepsins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.27 (cathepsin S); EC 3.4.22.43 (CTSL2 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180114
[Lr] Data última revisão:
180114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  7 / 15176 MEDLINE  
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[PMID]:29220410
[Au] Autor:Qiu Y; Ye X; Zhang HM; Hanson P; Zhao G; Tong L; Xie R; Yang D
[Ad] Endereço:Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
[Ti] Título:Cleavage of osmosensitive transcriptional factor NFAT5 by Coxsackieviral protease 2A promotes viral replication.
[So] Source:PLoS Pathog;13(12):e1006744, 2017 Dec.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nuclear factor of activated T cells 5 (NFAT5)/Tonicity enhancer binding protein (TonEBP) is a transcription factor induced by hypertonic stress in the kidney. However, the function of NFAT5 in other organs has rarely been studied, even though it is ubiquitously expressed. Indeed, although NFAT5 was reported to be critical for heart development and function, its role in infectious heart diseases has remained obscure. In this study, we aimed to understand the mechanism by which NFAT5 interferes with infection of Coxsackievirus B3 (CVB3), a major cause of viral myocarditis. Our initial results demonstrated that although the mRNA level of NFAT5 remained constant during CVB3 infection, NFAT5 protein level decreased because the protein was cleaved. Bioinformatic prediction and verification of the predicted site by site-directed mutagenesis experiments determined that the NFAT5 protein was cleaved by CVB3 protease 2A at Glycine 503. Such cleavage led to the inactivation of NFAT5, and the 70-kDa N-terminal cleavage product (p70-NFAT5) exerted a dominant negative effect on the full-length NFAT5 protein. We further showed that elevated expression of NFAT5 to counteract viral protease cleavage, especially overexpression of a non-cleavable mutant of NFAT5, significantly inhibited CVB3 replication. Ectopic expression of NFAT5 resulted in elevated expression of inducible nitric oxide synthase (iNOS), a factor reported to inhibit CVB3 replication. The necessity of iNOS for the anti-CVB3 effect of NFAT5 was supported by the observation that inhibition of iNOS blocked the anti-CVB3 effect of NFAT5. In a murine model of viral myocarditis, we observed that treatment with hypertonic saline or mannitol solution upregulated NFAT5 and iNOS expression, inhibited CVB3 replication and reduced tissue damage in the heart. Taken together, our data demonstrate that the anti-CVB3 activity of NFAT5 is impaired during CVB3 infection due to 2A-mediated cleavage of NFAT5. Thus induction of NFAT5 by hypertonic agents may be a promising strategy for the development of anti-CVB3 therapeutics.
[Mh] Termos MeSH primário: Infecções por Coxsackievirus/virologia
Cisteína Endopeptidases/metabolismo
Enterovirus Humano B/enzimologia
Miocardite/virologia
Miócitos Cardíacos/virologia
Fatores de Transcrição/metabolismo
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Linhagem Celular
Infecções por Coxsackievirus/imunologia
Infecções por Coxsackievirus/metabolismo
Infecções por Coxsackievirus/patologia
Enterovirus Humano B/imunologia
Enterovirus Humano B/fisiologia
Regulação da Expressão Gênica
Seres Humanos
Masculino
Camundongos Endogâmicos A
Mutação
Miocardite/imunologia
Miocardite/metabolismo
Miocardite/patologia
Miócitos Cardíacos/imunologia
Miócitos Cardíacos/metabolismo
Miócitos Cardíacos/patologia
Óxido Nítrico Sintase Tipo II/antagonistas & inibidores
Óxido Nítrico Sintase Tipo II/química
Óxido Nítrico Sintase Tipo II/genética
Óxido Nítrico Sintase Tipo II/metabolismo
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Proteólise
Interferência de RNA
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Especificidade por Substrato
Fatores de Transcrição/antagonistas & inibidores
Fatores de Transcrição/química
Fatores de Transcrição/genética
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NFAT5 protein, human); 0 (Nfat5 protein, mouse); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Transcription Factors); 0 (Viral Proteins); EC 1.14.13.39 (NOS2 protein, human); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.29 (picornain 2A, Picornavirus)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006744


  8 / 15176 MEDLINE  
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[PMID]:29228007
[Au] Autor:Thomas RG; Rivera Reyes BM; Gaston BM; Rivera Acosta NB; Bederman IR; Smith LA; Sutton MT; Wang B; Hunt JF; Bonfield TL
[Ad] Endereço:Department of Pediatrics, Division of Pulmonology, University Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.
[Ti] Título:Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1.
[So] Source:PLoS One;12(12):e0188614, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure. OBJECTIVE: We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens. METHODS: 3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1. RESULTS: Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05). CONCLUSION: These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1.
[Mh] Termos MeSH primário: Acetaminofen/química
Antígenos de Dermatophagoides/imunologia
Proteínas de Artrópodes/imunologia
Cisteína Endopeptidases/imunologia
Monócitos/imunologia
Nitratos/química
[Mh] Termos MeSH secundário: Animais
Antígenos de Dermatophagoides/química
Proteínas de Artrópodes/química
Asma/imunologia
Cisteína Endopeptidases/química
Dermatophagoides pteronyssinus/imunologia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Dermatophagoides); 0 (Arthropod Proteins); 0 (Nitrates); 362O9ITL9D (Acetaminophen); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.- (Dermatophagoides pteronyssinus antigen p 1)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188614


  9 / 15176 MEDLINE  
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[PMID]:29179951
[Au] Autor:Lv W; Sui L; Yan X; Xie H; Jiang L; Geng C; Li Q; Yao X; Kong Y; Cao J
[Ad] Endereço:Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
[Ti] Título:ROS-dependent Atg4 upregulation mediated autophagy plays an important role in Cd-induced proliferation and invasion in A549 cells.
[So] Source:Chem Biol Interact;279:136-144, 2018 Jan 05.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cadmium (Cd) is a toxic heavy metal that is widely used in industry and agriculture. In this study the role of autophagy in Cd-induced proliferation, migration and invasion was investigated in A549 cells. Exposure to Cd (2 µM) significantly increased reactive oxygen species (ROS) production, induced autophagy and enhanced cell growth, migration and invasion in A549 cells. Western blot analysis showed that the expression of autophagy-related proteins, LC3-II, Beclin-1 and Atg4 and invasion-related protein MMP-9 were upregulated in Cd-treated cells. N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of A549 cells and the increasing protein level of LC3-II and Atg4. Blocking Atg4 expression by siRNA strongly reduced Beclin-1 and LC3-II protein expression and the number of autophagosome positive cells induced by Cd. Furthermore, Atg4 siRNA increased the number of cells at G0/G1 phase, reduced the number of S and G2/M phase cells, and inhibited Cd-induced cell growth significantly compared with that of Cd-treated Control siRNA cells. 3-MA pretreatment increased the percentage of G0/G1 phase cells, decreased S phase and G2/M phase percentage, and inhibited Cd-induced cell growth remarkably compared with that of only Cd-treated cells. Knocking down Atg4 reduced the number of cells that migrated and invaded through the Matrigel matrix significantly and led to a significant decrease of MMP-9 expression. In addition, in lung tissues of Cd-treated BALB/c mice, the increased expression of LC3-II, Beclin-1 and Atg4 were observed. Taken together, our results demonstrated that ROS-dependent Atg4-mediated autophagy plays an important role in Cd-induced cell growth, migration and invasion in A549 cells.
[Mh] Termos MeSH primário: Adenocarcinoma/metabolismo
Proteínas Relacionadas à Autofagia/metabolismo
Autofagia/efeitos dos fármacos
Cádmio/farmacologia
Cisteína Endopeptidases/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Relacionadas à Autofagia/genética
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Cisteína Endopeptidases/genética
Seres Humanos
Invasividade Neoplásica
Espécies Reativas de Oxigênio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autophagy-Related Proteins); 0 (Reactive Oxygen Species); 00BH33GNGH (Cadmium); EC 3.4.22.- (ATG4A protein, human); EC 3.4.22.- (Cysteine Endopeptidases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180103
[Lr] Data última revisão:
180103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE


  10 / 15176 MEDLINE  
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[PMID]:29227928
[Au] Autor:Damalanka VC; Kim Y; Galasiti Kankanamalage AC; Rathnayake AD; Mehzabeen N; Battaile KP; Lovell S; Nguyen HN; Lushington GH; Chang KO; Groutas WC
[Ad] Endereço:Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
[Ti] Título:Structure-guided design, synthesis and evaluation of oxazolidinone-based inhibitors of norovirus 3CL protease.
[So] Source:Eur J Med Chem;143:881-890, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Acute nonbacterial gastroenteritis caused by noroviruses constitutes a global public health concern and a significant economic burden. There are currently no small molecule therapeutics or vaccines for the treatment of norovirus infections. A structure-guided approach was utilized in the design of a series of inhibitors of norovirus 3CL protease that embody an oxazolidinone ring as a novel design element for attaining optimal binding interactions. Low micromolar cell-permeable inhibitors that display anti-norovirus activity have been identified. The mechanism of action, mode of binding, and structural rearrangements associated with the interaction of the inhibitors and the enzyme were elucidated using X-ray crystallography.
[Mh] Termos MeSH primário: Norovirus/enzimologia
Oxazolidinonas/farmacologia
Inibidores de Proteases/farmacologia
Proteínas Virais/antagonistas & inibidores
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Cisteína Endopeptidases/metabolismo
Relação Dose-Resposta a Droga
Modelos Moleculares
Estrutura Molecular
Oxazolidinonas/síntese química
Oxazolidinonas/química
Inibidores de Proteases/síntese química
Inibidores de Proteases/química
Relação Estrutura-Atividade
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oxazolidinones); 0 (Protease Inhibitors); 0 (Viral Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.28 (3C proteases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE



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