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[PMID]:27911604
[Au] Autor:Chalmers JD; Moffitt KL; Suarez-Cuartin G; Sibila O; Finch S; Furrie E; Dicker A; Wrobel K; Elborn JS; Walker B; Martin SL; Marshall SE; Huang JT; Fardon TC
[Ad] Endereço:1 Scottish Centre for Respiratory Research and.
[Ti] Título:Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis.
[So] Source:Am J Respir Crit Care Med;195(10):1384-1393, 2017 May 15.
[Is] ISSN:1535-4970
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis. METHODS: This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography-confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years. MEASUREMENT AND MAIN RESULTS: Elastase activity in sputum was associated with the bronchiectasis severity index (r = 0.49; P < 0.0001) and was also correlated with the Medical Research Council dyspnea score (r = 0.34; P < 0.0001), FEV % predicted (r = -0.33; P < 0.0001), and the radiological extent of bronchiectasis (r = 0.29; P < 0.0001). During a 3-year follow-up, elevated sputum elastase activity was associated with a higher frequency of exacerbations (P < 0.0001) but was not independently associated with mortality. Sputum elastase activity was independently associated with FEV decline (ß coefficient, -0.139; P = 0.001). Elastase showed good discrimination for severe exacerbations with an area under the curve of 0.75 (95% confidence interval [CI], 0.72-0.79) and all-cause mortality (area under the curve, 0.70; 95% CI, 0.67-0.73). Sputum elastase activity increased at exacerbations (P = 0.001) and was responsive to treatment with antibiotics. Desmosine was correlated with sputum elastase (r = 0.42; P < 0.0001) and was associated with risk of severe exacerbations (hazard ratio 2.7; 95% CI, 1.42-5.29; P = 0.003) but not lung function decline. CONCLUSIONS: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.
[Mh] Termos MeSH primário: Bronquiectasia/metabolismo
Bronquiectasia/fisiopatologia
Elastase de Leucócito/metabolismo
Pulmão/fisiopatologia
[Mh] Termos MeSH secundário: Idoso
Biomarcadores/metabolismo
Estudos de Coortes
Desmosina/metabolismo
Progressão da Doença
Feminino
Seres Humanos
Pulmão/metabolismo
Masculino
Meia-Idade
Neutrófilos/metabolismo
Estudos Prospectivos
Sistema de Registros
Índice de Gravidade de Doença
Escarro/metabolismo
Reino Unido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 11003-57-9 (Desmosine); EC 3.4.21.37 (Leukocyte Elastase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE
[do] DOI:10.1164/rccm.201605-1027OC


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[PMID]:27916391
[Au] Autor:Naffa R; Holmes G; Ahn M; Harding D; Norris G
[Ad] Endereço:Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand. Electronic address: r.naffa@massey.ac.nz.
[Ti] Título:Liquid chromatography-electrospray ionization mass spectrometry for the simultaneous quantitation of collagen and elastin crosslinks.
[So] Source:J Chromatogr A;1478:60-67, 2016 Dec 23.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We have developed a novel chromatographic analytical method for the simultaneous quantitation of collagen crosslinks. Seven non-derivatised crosslinks could be separated on a Cogent Diamond Hydride HPLC column using either isocratic or gradient conditions then detected by mass spectrometry. The total run time was less than 10min which is significantly shorter than that previously reported. This is the first method in which histidinohydroxylysinonorleucine (HHL) and histidinohydroxymero-desmosine (HHMD) were separated and identified by mass spectrometry without the need for pre- or post-column derivatization. The CVs of the retention times of all seven crosslinks were less than 1% and the limit of detection (LOD) and the limits of quantitation (LOQ) were 0.07-0.13pmol/µL and 0.20-0.38pmol/µL, respectively. This novel method was used for the routine analysis and quantitation of crosslinks in different animal skins in which potential new collagen crosslinks were identified that are as yet undocumented.
[Mh] Termos MeSH primário: Técnicas de Química Analítica/métodos
Cromatografia Líquida
Colágeno/análise
Elastina/análise
Espectrometria de Massas por Ionização por Electrospray
[Mh] Termos MeSH secundário: Animais
Colágeno/química
Desmosina/isolamento & purificação
Dipeptídeos/isolamento & purificação
Elastina/química
Histidina/análogos & derivados
Histidina/isolamento & purificação
Limite de Detecção
Pele/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dipeptides); 0 (histidinohydroxylysinonorleucine); 11003-57-9 (Desmosine); 4QD397987E (Histidine); 9007-34-5 (Collagen); 9007-58-3 (Elastin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161206
[St] Status:MEDLINE


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[PMID]:26601954
[Au] Autor:Pilecki B; Holm AT; Schlosser A; Moeller JB; Wohl AP; Zuk AV; Heumüller SE; Wallis R; Moestrup SK; Sengle G; Holmskov U; Sorensen GL
[Ad] Endereço:From the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, 5000 Odense C, Denmark.
[Ti] Título:Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation.
[So] Source:J Biol Chem;291(3):1103-14, 2016 Jan 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:MFAP4 (microfibrillar-associated protein 4) is an extracellular glycoprotein found in elastic fibers without a clearly defined role in elastic fiber assembly. In the present study, we characterized molecular interactions between MFAP4 and elastic fiber components. We established that MFAP4 primarily assembles into trimeric and hexameric structures of homodimers. Binding analysis revealed that MFAP4 specifically binds tropoelastin and fibrillin-1 and -2, as well as the elastin cross-linking amino acid desmosine, and that it co-localizes with fibrillin-1-positive fibers in vivo. Site-directed mutagenesis disclosed residues Phe(241) and Ser(203) in MFAP4 as being crucial for type I collagen, elastin, and tropoelastin binding. Furthermore, we found that MFAP4 actively promotes tropoelastin self-assembly. In conclusion, our data identify MFAP4 as a new ligand of microfibrils and tropoelastin involved in proper elastic fiber organization.
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Desmosina/metabolismo
Tecido Elástico/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Glicoproteínas/metabolismo
Microfibrilas/metabolismo
Proteínas dos Microfilamentos/metabolismo
Modelos Moleculares
Tropoelastina/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Proteínas de Transporte/química
Proteínas de Transporte/genética
Proteínas da Matriz Extracelular/química
Proteínas da Matriz Extracelular/genética
Fibrilina-1
Fibrilinas
Glicoproteínas/química
Glicoproteínas/genética
Seres Humanos
Ligantes
Masculino
Camundongos Endogâmicos C57BL
Camundongos Mutantes
Proteínas dos Microfilamentos/química
Proteínas dos Microfilamentos/genética
Mutação
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Domínios e Motivos de Interação entre Proteínas
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Multimerização Proteica
Transporte Proteico
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Tropoelastina/química
Tropoelastina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Extracellular Matrix Proteins); 0 (FBN1 protein, human); 0 (Fbn1 protein, mouse); 0 (Fibrillin-1); 0 (Fibrillins); 0 (Glycoproteins); 0 (Ligands); 0 (MFAP4 protein, human); 0 (MFAP4 protein, mouse); 0 (Microfilament Proteins); 0 (Peptide Fragments); 0 (Protein Isoforms); 0 (Recombinant Proteins); 0 (Tropoelastin); 11003-57-9 (Desmosine)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170118
[Lr] Data última revisão:
170118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151126
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.681775


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[PMID]:26307084
[Au] Autor:Zhang J; Yang R; Liu Z; Hou C; Zong W; Zhang A; Sun X; Gao J
[Ad] Endereço:Institute of Developmental Biology, School of Life Science, Shandong University, 27 Shanda Nanlu, Jinan 250100, China.
[Ti] Título:Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.
[So] Source:Hum Mol Genet;24(21):6174-85, 2015 Nov 01.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In mammals, embryonic development are highly regulated morphogenetic processes that are tightly controlled by genetic elements. Failure of any one of these processes can result in embryonic malformation. The lysyl oxidase (LOX) family genes are closely related to human diseases. In this study, we investigated the essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the deletion of the Loxl3 gene led to impaired development of the palate shelves, abnormalities in the cartilage primordia of the thoracic vertebrae and mild alveolar shrinkage. We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of LOXL3 resulted in cleft palate and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is indispensable for mouse palatogenesis and vertebral column development. The Loxl3 gene may be a candidate disease gene resulting in cleft palate and spinal deformity.
[Mh] Termos MeSH primário: Aminoácido Oxirredutases/fisiologia
Fissura Palatina/embriologia
Desenvolvimento Embrionário/fisiologia
Coluna Vertebral/anormalidades
[Mh] Termos MeSH secundário: Aminoácido Oxirredutases/biossíntese
Aminoácido Oxirredutases/genética
Animais
Aorta/patologia
Colágeno/metabolismo
Anormalidades Craniofaciais/genética
Desmosina/metabolismo
Diafragma/patologia
Olho/metabolismo
Olho/patologia
Marcação de Genes
Hidroxiprolina/metabolismo
Pulmão/patologia
Camundongos
Camundongos Endogâmicos C57BL
Miocárdio/patologia
Palato/metabolismo
Vértebras Torácicas/embriologia
Traqueia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
11003-57-9 (Desmosine); 9007-34-5 (Collagen); EC 1.4.- (Amino Acid Oxidoreductases); EC 1.4.3.- (LOXL3 protein, mouse); RMB44WO89X (Hydroxyproline)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151015
[Lr] Data última revisão:
151015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150827
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddv333


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[PMID]:25917031
[Au] Autor:Yang Y; Guo Y; Zhang H; Sun T
[Ad] Endereço:Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing 100730, China.
[Ti] Título:[Desmosine plasma levels and exacerbation risk assessment of chronic obstructive pulmonary disease].
[So] Source:Zhonghua Yi Xue Za Zhi;95(8):577-80, 2015 Mar 03.
[Is] ISSN:0376-2491
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To explore the relationship between desmosine plasma levels and exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). METHODS: COPD patients and normal subjects were recruited from Beijing Hospital during March 2013 to March 2014. COPD patients were divided into COPD low risk and COPD high risk groups according to the criteria of Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy. The plasma concentrations of desmosine were measured by enzyme-linked immunosorbent assay (ELISA) for exploring the inter-group difference in desmosine levels. RESULTS: Sixty-three COPD patients (COPD low risk group, n = 30; COPD high risk group, n = 33) and 50 normal subjects (24 healthy non-smokers, 26 healthy smokers) were recruited. The plasma desmosine concentrations in healthy non-smokers, healthy smokers, low risk and high risk COPD patients were (200 ± 159), (191 ± 105), (197 ± 118) and (131 ± 47) ng/L respectively. The plasma concentration of desmosine was significantly lower in COPD high risk group than healthy non-smokers (mean difference -70, 95%CI: -128--11, P = 0.021), healthy smokers (mean difference -60, 95%CI: -118--3, P = 0.039) and COPD low risk group (mean difference -67, 95%CI: -122--12, P = 0.018). The plasma concentration of desmosine was negatively correlated with exacerbation frequency (r = -0.409, P = 0.002), mMRC scores (r = -0.447, P = 0.010) and emphysema severity (r = -0.386, P = 0.047) in COPD patients. No significant correlation existed between desmosine plasma levels and forced expiratory volume in one second (FEV1%pred) in COPD patients (r = 0.225, P = 0.084). CONCLUSIONS: The plasma levels of desmosine are lower in high risk COPD patients than those in normal subjects or low risk COPD patients. And it is negatively correlated with exacerbation frequency in COPD patients.
[Mh] Termos MeSH primário: Doença Pulmonar Obstrutiva Crônica
[Mh] Termos MeSH secundário: Desmosina
Ensaio de Imunoadsorção Enzimática
Volume Expiratório Forçado
Seres Humanos
Enfisema Pulmonar
Medição de Risco
Fumar
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
11003-57-9 (Desmosine)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:150428
[Lr] Data última revisão:
150428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150429
[St] Status:MEDLINE


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[PMID]:25890800
[Au] Autor:Tanigawa T; Komatsu A; Usuki T
[Ad] Endereço:Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
[Ti] Título:[(13)C3,(15)N1]-labeled isodesmosine: A potential internal standard for LC-MS/MS analysis of desmosines in elastin degradation.
[So] Source:Bioorg Med Chem Lett;25(10):2046-9, 2015.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Isodesmosine and desmosine are crosslinking amino acids that are present only in elastin. They are useful biomarkers for the degradation of elastin, which occurs during the progression of chronic obstructive pulmonary disease (COPD) and related diseases. This Letter describes the synthesis of [(13)C3,(15)N1]-labeled isodesmosine, using Chichibabin pyridine synthesis as a key reaction. The labeled isodesmosine is a potential internal standard for the quantitative LC-MS/MS analysis of desmosines in elastin degradation.
[Mh] Termos MeSH primário: Cromatografia Líquida
Desmosina/análise
Elastina/metabolismo
Isodesmosina/síntese química
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Isótopos de Carbono/análise
Elastina/química
Isodesmosina/química
Estrutura Molecular
Isótopos de Nitrogênio/análise
Doença Pulmonar Obstrutiva Crônica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Carbon Isotopes); 0 (Nitrogen Isotopes); 11003-57-9 (Desmosine); 9007-58-3 (Elastin); 991-01-5 (Isodesmosine)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150430
[Lr] Data última revisão:
150430
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150420
[St] Status:MEDLINE


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[PMID]:25855762
[Au] Autor:Sampedro I; Kato J; Hill JE
[Ad] Endereço:1​ Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
[Ti] Título:Elastin degradation product isodesmosine is a chemoattractant for Pseudomonas aeruginosa.
[So] Source:Microbiology;161(7):1496-503, 2015 Jul.
[Is] ISSN:1465-2080
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Previous studies have demonstrated that Pseudomonas aeruginosa PAO1 is chemotactic towards proteinogenic amino acids, however, the chemotaxis response of this strain towards non-proteinogenic amino acids and the specific chemoreceptors involved in this response are essentially unknown. In this study, we analysed the chemotactic response of PAO1 towards two degradation products of elastin, the lysine-rich, non-proteinogenic amino acids, desmosine and isodesmosine. We observed that isodesmosine, a potential biomarker for different diseases, served as a chemoattractant for PAO1. A screen of 251methyl-accepting chemotaxis proteins mutants of PAO1 identified PctA as the chemoreceptor for isodesmosine. We also showed that the positive chemotactic response to isodesmosine is potentially common by demonstrating chemoattraction in 12 of 15 diverse (in terms of source of isolation) clinical isolates, suggesting that the chemotactic response to this non-proteinogenic amino acid might be a conserved feature of acute infection isolates and thus could influence the colonization of potential infection sites.
[Mh] Termos MeSH primário: Fatores Quimiotáticos/metabolismo
Quimiotaxia
Elastina/metabolismo
Isodesmosina/metabolismo
Pseudomonas aeruginosa/efeitos dos fármacos
Pseudomonas aeruginosa/fisiologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Desmosina/metabolismo
Seres Humanos
Infecções por Pseudomonas/microbiologia
Pseudomonas aeruginosa/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Chemotactic Factors); 0 (PctA protein, Pseudomonas aeruginosa); 11003-57-9 (Desmosine); 9007-58-3 (Elastin); 991-01-5 (Isodesmosine)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:150828
[Lr] Data última revisão:
150828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150410
[St] Status:MEDLINE
[do] DOI:10.1099/mic.0.000090


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[PMID]:25790295
[Au] Autor:Lunghi B; De Cunto G; Cavarra E; Fineschi S; Bartalesi B; Lungarella G; Lucattelli M
[Ad] Endereço:Department of Life Sciences, Section of Experimental Pathology, University of Siena, Siena, Italy.
[Ti] Título:Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema.
[So] Source:PLoS One;10(3):e0119797, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a). The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis. We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure. No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS. Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells. Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli. Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis. The blockage of apoptosis interferes with the macrophage "clearance" from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells. The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes. Macrophages from smoking p66Shc-/- mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas. We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory response to CS exposure.
[Mh] Termos MeSH primário: Bronquiolite/etiologia
Bronquiolite/genética
Fibrose/genética
Proteínas Adaptadoras da Sinalização Shc/genética
Fumar/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Apoptose
Arginase/metabolismo
Bronquiolite/patologia
Quitinases/metabolismo
Desmosina/metabolismo
Hidroxiprolina/metabolismo
Interleucina-13/metabolismo
Interleucina-4/metabolismo
Pulmão/metabolismo
Pulmão/patologia
Macrófagos/enzimologia
Macrófagos/metabolismo
Camundongos
Camundongos Knockout
Estresse Oxidativo
Oxirredutases/metabolismo
Enfisema Pulmonar/patologia
Proteínas Adaptadoras da Sinalização Shc/deficiência
Proteínas Adaptadoras da Sinalização Shc/metabolismo
Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src
Fator de Crescimento Transformador beta/genética
Fator de Crescimento Transformador beta/metabolismo
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Interleukin-13); 0 (Shc Signaling Adaptor Proteins); 0 (Shc1 protein, mouse); 0 (Src Homology 2 Domain-Containing, Transforming Protein 1); 0 (Transforming Growth Factor beta); 0 (Tumor Suppressor Protein p53); 11003-57-9 (Desmosine); 207137-56-2 (Interleukin-4); EC 1.- (Oxidoreductases); EC 3.2.1.14 (Chitinases); EC 3.5.3.1 (Arg1 protein, mouse); EC 3.5.3.1 (Arginase); RMB44WO89X (Hydroxyproline)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150320
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0119797


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[PMID]:25762453
[Au] Autor:Liu X; Ma S; Liu S; Liu M; Turino G; Cantor J
[Ad] Endereço:St John's University, New York, NY, USA.
[Ti] Título:The Ratio of Free to Bound Desmosine and Isodesmosine May Reflect Emphysematous Changes in COPD.
[So] Source:Lung;193(3):329-34, 2015 Jun.
[Is] ISSN:1432-1750
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The unique elastin crosslinks, desmosine and isodesmosine (DID) are significantly elevated in blood, urine, and sputum from patients with COPD, and may decline following treatment of the disease. However, the large degree of variance in this biomarker among COPD patients with similar levels of disease suggests that it has limited prognostic value with regard to the degree of lung disease in a given individual. As an alternative to measuring the total amount of DID, we propose using the ratio of free to peptide-bound DID, which may provide a better indication of overall lung disease. METHODS: To test this hypothesis, the free/bound DID ratio was measured in bronchoalveolar lavage fluid (BALF) from both hamsters with elastase-induced emphysema and controls not given the enzyme, using a combination of liquid chromatography and tandem mass spectroscopy. This ratio was then correlated with airspace enlargement, as measured by the mean percentage of lung surface area at ×100 microscopic magnification. RESULTS: There was a significant negative correlation between the free/bound DID ratio in BALF and lung surface area. However, there was no correlation between this ratio and total BALF DID, suggesting that free/bound DID is unrelated to the immediate rate of breakdown of elastic fibers, and may instead measure the cumulative effect of elastase injury in the lung. CONCLUSIONS: The free/bound DID ratio may be a useful measure of emphysematous changes in the lung and might also serve as a screening procedure for healthy smokers and other individuals at risk for developing COPD.
[Mh] Termos MeSH primário: Desmosina/metabolismo
Isodesmosina/metabolismo
Pulmão/metabolismo
Doença Pulmonar Obstrutiva Crônica/metabolismo
Enfisema Pulmonar/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Líquido da Lavagem Broncoalveolar/química
Cromatografia Líquida
Modelos Animais de Doenças
Feminino
Mesocricetus
Elastase Pancreática
Valor Preditivo dos Testes
Doença Pulmonar Obstrutiva Crônica/diagnóstico
Enfisema Pulmonar/induzido quimicamente
Enfisema Pulmonar/diagnóstico
Índice de Gravidade de Doença
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 11003-57-9 (Desmosine); 991-01-5 (Isodesmosine); EC 3.4.21.36 (Pancreatic Elastase)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150313
[St] Status:MEDLINE
[do] DOI:10.1007/s00408-015-9712-z


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[PMID]:25604393
[Au] Autor:Schräder CU; Heinz A; Majovsky P; Schmelzer CE
[Ad] Endereço:Institute of Pharmacy, Faculty of Natural Sciences I, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
[Ti] Título:Fingerprinting desmosine-containing elastin peptides.
[So] Source:J Am Soc Mass Spectrom;26(5):762-73, 2015 May.
[Is] ISSN:1879-1123
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble precursor tropoelastin, which is subsequently cross-linked in the course of the elastic fiber assembly. The process involves the formation of the two tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are unique to elastin. The resulting high degree of cross-linking confers remarkable properties, including mechanical integrity, insolubility, and long-term stability to the protein. These characteristics hinder the structural elucidation of mature elastin. However, MS(2) data of linear and cross-linked peptides released by proteolysis can provide indirect insights into the structure of elastin. In this study, we performed energy-resolved collision-induced dissociation experiments of DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine characteristic product ions. It was found that all investigated compounds yielded the same product ion clusters at elevated collision energies. Elemental composition determination using the exact masses of these ions revealed molecular formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES remains intact even at relatively high collision energies. The finding of these specific product ions enabled the development of a similarity-based scoring algorithm that was successfully applied on LC-MS/MS data of bovine elastin digests for the identification of DES-/IDES-cross-linked peptides. This approach facilitates the straightforward investigation of native cross-links in elastin.
[Mh] Termos MeSH primário: Desmosina/análise
Elastina/química
Isodesmosina/análise
Modelos Moleculares
Fragmentos de Peptídeos/análise
Tropoelastina/química
[Mh] Termos MeSH secundário: Animais
Bovinos
Cromatografia Líquida de Alta Pressão
Reagentes para Ligações Cruzadas/química
Desmosina/química
Seres Humanos
Isodesmosina/química
Estrutura Molecular
Peso Molecular
Oligopeptídeos/análise
Oligopeptídeos/química
Fragmentos de Peptídeos/química
Mapeamento de Peptídeos
Estabilidade Proteica/efeitos dos fármacos
Proteólise
Espectrometria de Massas por Ionização por Electrospray
Estereoisomerismo
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (Oligopeptides); 0 (Peptide Fragments); 0 (Tropoelastin); 11003-57-9 (Desmosine); 9007-58-3 (Elastin); 991-01-5 (Isodesmosine)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150122
[St] Status:MEDLINE
[do] DOI:10.1007/s13361-014-1075-9



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