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The American Review of Respiratory... Mar 1984
Topics: Amino Acids; Desmosine; Elastic Tissue; Humans; Lung Diseases; Smoking
PubMed: 6703512
DOI: 10.1164/arrd.1984.129.3.511c -
Journal of Separation Science Feb 2007Desmosines are crosslinking amino acids unique to mature elastin in humans. Owing to this unicity, they have been discussed as potentially attractive indicators of... (Review)
Review
Desmosines are crosslinking amino acids unique to mature elastin in humans. Owing to this unicity, they have been discussed as potentially attractive indicators of connective tissue disorders whose clinical manifestations are mostly the result of elastin degradation. This review covers advances in immunochemical, chromatographic, and electrophoretic procedures applied in the last 25 years to detect and quantitate these crosslinksin a variety of biological samples. Recent applications of CE with LIF detection (CE-LIF) for investigating the content of desmosines in different fluids will also be discussed.
Topics: Amino Acids; Animals; Biomarkers; Desmosine; Elastin; Humans; Immunochemistry; Isodesmosine
PubMed: 17390614
DOI: 10.1002/jssc.200600260 -
Bioorganic & Medicinal Chemistry Dec 2021Desmosine and isodesmosine are crosslinking amino acids of elastin, which is an essential component of the dermal extracellular matrix protein. Quantitative analysis of...
Desmosine and isodesmosine are crosslinking amino acids of elastin, which is an essential component of the dermal extracellular matrix protein. Quantitative analysis of crosslinker desmosines in human skin dermis has not been fully achieved due to the insoluble nature of elastin protein. In the present study, chemical synthesis of isotopically labeled desmosine, desmosine-C,N, was carried out via isoChichibabin pyridinium synthesis starting from corresponding isotopically labeled amino acids. Isotope-dilution LC-MS/MS analysis of desmosine and isodesmosine utilizing synthetic desmosine-C,N enabled the quantitative analysis of desmosines in human skin for the first time. Thus, ca. 1.43 μg of desmosines was detected from analysis of 1 mg of dry human skin.
Topics: Carbon Isotopes; Chromatography, Liquid; Desmosine; Humans; Isodesmosine; Molecular Structure; Nitrogen Isotopes; Skin; Tandem Mass Spectrometry
PubMed: 34839160
DOI: 10.1016/j.bmc.2021.116519 -
Scientific Reports 2013We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid...
We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.
Topics: Biocompatible Materials; Cross-Linking Reagents; Desmosine; Hyaluronic Acid; Hydrogels; Materials Testing; Mechanical Phenomena; Molecular Structure; Tissue Engineering
PubMed: 23784477
DOI: 10.1038/srep02043 -
[Desmosine plasma levels and exacerbation risk assessment of chronic obstructive pulmonary disease].Zhonghua Yi Xue Za Zhi Mar 2015To explore the relationship between desmosine plasma levels and exacerbation risk in patients with chronic obstructive pulmonary disease (COPD).
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.
Topics: Desmosine; Enzyme-Linked Immunosorbent Assay; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Risk Assessment; Smoking
PubMed: 25917031
DOI: No ID Found -
Lung Dec 2018While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary...
PURPOSE
While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary emphysema, the usefulness of DID in detecting early lung injury remains untested. To this end, our laboratory has measured DID in a hamster model of smoke-induced emphysema, involving only minimal alveolar wall damage.
METHODS
Animals were either treated with cigarette smoke for 2 h/day, 5 days/week, or exposed only to room air (controls) for a period of 3 months. DID levels in bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly intervals, using liquid chromatography and tandem mass spectrometry. Lung surface area was also determined, as a measure of airspace enlargement.
RESULTS
The portion of BALF DID not bound to peptides (free DID) was significantly higher in smoke-exposed animals at 2 months (9.2 vs 4.4 pg/mg protein; p < 0.05), whereas total BALF DID showed no significant increases over the course of the study, and total lung DID remained unchanged. There was a mild, but significant, loss of lung surface area in the smoke-exposed group at 2 months (28.8% vs 25.2%, p < 0.05), which showed no further progression, consistent with the return of free DID to control levels at 3 months.
CONCLUSIONS
These findings support the hypothesis that free DID are sensitive indicators of smoke-induced lung injury. Measurement of free DID in smokers with minimally decreased lung mass may help determine the utility of this parameter as a test for incipient pulmonary emphysema.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Chromatography, Liquid; Desmosine; Disease Models, Animal; Female; Lung; Mesocricetus; Pulmonary Emphysema; Smoking; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Time Factors; Up-Regulation
PubMed: 30218154
DOI: 10.1007/s00408-018-0163-1 -
Respiratory Research Mar 2018Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial...
Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.
Topics: Aged; Aging; Biomarkers; Desmosine; Elastin; Female; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive
PubMed: 29558926
DOI: 10.1186/s12931-018-0747-6 -
Respirology (Carlton, Vic.) Feb 2018Matrix degradation is a key feature of chronic obstructive pulmonary disease (COPD). Desmosine and isodesmosine (desmosines) are excreted in urine following matrix...
BACKGROUND AND OBJECTIVE
Matrix degradation is a key feature of chronic obstructive pulmonary disease (COPD). Desmosine and isodesmosine (desmosines) are excreted in urine following matrix degradation. The main purpose of this study was to investigate the association between computed tomography (CT) emphysema indices and urinary desmosines in patients with COPD.
METHODS
A total of 152 subjects were selected from the Korean Obstructive Lung Disease cohort. Their urine samples were assayed for desmosines using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The cohort was divided into emphysema-dominant (n = 80) and non-emphysema dominant- (n = 72) groups according to the CT emphysema index.
RESULTS
The level of urinary desmosines was significantly higher in the emphysema-dominant group. Significant differences were also observed between the two groups for body mass index and lung function. Multivariate analysis indicated that a high level of urinary desmosines was a significant independent predictor of emphysema (relative risk: 2.6; 95% CI: 1.11-6.09; P = 0.028). The percentage of frequent exacerbators was significantly higher in the high urinary desmosine group in the first year of follow-up (P = 0.041). The mean number of exacerbations was higher in the high urinary desmosine group, although this difference was not statistically significant (P = 0.067). The changes in emphysema index did not differ between the two urinary desmosine groups over 3 years of follow-up.
CONCLUSION
This study indicates that the level of urinary desmosines measured by LC-MS/MS methods is associated with the CT emphysema index. Urinary desmosine can be a useful predictor in identifying frequent exacerbators.
Topics: Aged; Biomarkers; Cohort Studies; Desmosine; Female; Humans; Isodesmosine; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 28905464
DOI: 10.1111/resp.13170 -
The American Review of Respiratory... Nov 1980Desmosine is a cross-link amino acid unique to elastin. Previous work has shown that during turnover in the body, desmosine is not reused, and that desmosine is not...
Desmosine is a cross-link amino acid unique to elastin. Previous work has shown that during turnover in the body, desmosine is not reused, and that desmosine is not absorbed from the intestine. Instead, all desmosine released in the course of elastin metabolism is excreted in the urine attached to low molecular weight peptides. Therefore, measurement of desmosine in acid-hydrolysates of urine might be used to monitor elastin breakdown in several pathologic states, including pulmonary emphysema. In the present report, we have described a sensitive, highly specific radioimmunoassay capable of detecting as little as 200 pg of desmosine in acid-hydrolysates of urine. The assay was specific for desmosine; cross-reactivity with merodesmosine, isodesmosine, lysine, and mixed amino acids was 0.25%, 0.1%, less than 0.0003%, and 0%, respectively. Twenty-three normal, nonsmoking subjects had a mean 24-hr desmosine excretion of 47 +/- 15 microgram. In a group of smokers with evidence of chronic obstructive disease and/or lung infection, the values for desmosine excretion ranged from 40 to 400 microgram/24 h. Desmosine radioimmunoassay may find application in the study of diseases involving increased destruction of elastin in the body.
Topics: Adolescent; Adult; Aged; Amino Acids; Desmosine; Elastin; Humans; Lung Diseases, Obstructive; Middle Aged; Radioimmunoassay; Smoking
PubMed: 7447157
DOI: 10.1164/arrd.1980.122.5.769 -
Chest Dec 2009Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active...
BACKGROUND
Cystic fibrosis (CF) lung disease is characterized by structural changes in the airways and parenchyma. No sputum biomarker exists to measure the degree of active structural destruction during pulmonary exacerbation in patients with CF. The noninvasive measurement of desmosine, a breakdown product of elastin, may reflect ongoing lung injury and serve as a biomarker of short-term damage. Our objectives were to measure desmosine in the sputum of patients with CF hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine levels and other markers of clinical improvement, including lung function and inflammatory mediators, following hospitalization.
METHODS
Sputum and blood samples collected and lung function measurements were made at multiple time points during hospitalization. We used a repeated measures model, adjusted for age and time between measurements, to compare log-transformed sputum desmosine levels across multiple time points and to correlate those levels with related variables.
RESULTS
Desmosine levels were measured by radioimmunoassay in 71 expectorated sputum samples from 19 patients with CF hospitalized for 26 pulmonary exacerbations (range of results, 0 to 200 pmol/L desmosine/mL). Sputum desmosine levels decreased significantly during the first week of hospitalization (p = 0.04). Desmosine levels were positively associated with plasma C-reactive protein (rho = 0.59; p = 0.03), sputum interleukin-8 (rho = 0.86; p < 0.01), and sputum neutrophil elastase (rho = 0.78; p < 0.01).
CONCLUSIONS
Sputum desmosine, a novel measure of acute structural lung injury, may serve as a marker of structural lung damage occurring during exacerbations of lung disease in CF.
Topics: Adolescent; Adult; Biomarkers; C-Reactive Protein; Child; Cohort Studies; Cystic Fibrosis; Desmosine; Female; Hospitalization; Humans; Interleukin-8; Leukocyte Elastase; Lung; Male; Prospective Studies; Severity of Illness Index; Sputum; Young Adult
PubMed: 19567495
DOI: 10.1378/chest.09-0217