Progress in the methodological strategies for the detection in real samples of desmosine and isodesmosine, two biological markers of elastin degradation

Viglio, Simona; Annovazzi, Laura; Luisetti, Maurizio; Stolk, Jan; Casado, Begoña; Iadarola, Paolo

doi:10.1002/jssc.200600260

Cited by 28 publications

(17 citation statements)

References 91 publications

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“…Further improvement in the analysis was reported by the use of combined HPLC and liquid chromatography mass spectrometry (LC-MS) analysis [19], in which both DES and IDES can be determined separately with higher sensitivity and specificity. DES and IDES levels in normal urine (n57) obtained by the LC-MS analysis are 8 information about the different procedures so far applied to the determination of desmosines in different biological matrices has been recently published [20]; the procedures are also summarised in table 1.…”

Section: Elastin Breakdown Products and Methods Of Measurementmentioning

confidence: 99%

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

Luisetti¹,

Ma²,

Iadarola³

et al. 2008

European Respiratory Journal

114

110

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Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. In the present manuscript, immunology-based and separation methods for the evaluation of DES and IDES are discussed, along with studies reporting increased levels of urine excretion in chronic obstructive pulmonary disease (COPD) patients with and without a 1 -antitrypsin deficiency. The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.

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Section: Elastin Breakdown Products and Methods Of Measurementmentioning

confidence: 99%

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

Luisetti¹,

Ma²,

Iadarola³

et al. 2008

European Respiratory Journal

114

110

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“…In particular, the high sensitivity of Micellar Electrokinetic Chromatography with Laser Induced Fluorescence detection (MEKC-LIF), has proved successful in detecting these cross-links for the first time in serum and sputum as well [18]. The protocol was shown to work well with a variety of fluids from a large cohort of different subjects [19]. Derivatized endogenous desmosines were visualized after spiking the sample with FITC-labelled standard desmosines and their amount determined by reference of peak areas to a calibration plot [18].…”

Section: Introductionmentioning

confidence: 96%

Micellar Electrokinetic Chromatography with Laser Induced Detection and liquid chromatography tandem mass-spectrometry-based desmosine assays in urine of patients with Chronic Obstructive Pulmonary Disease: A comparative analysis

Ferrari¹,

Fumagalli

Piccinini³

et al. 2012

Journal of Chromatography A

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“…To be able to antagonize such processes, it is of great importance to better understand the structure of elastin, including the formation of its complex cross-linking pattern. In addition to these structural aspects, the screening for DES and IDES as potential biomarkers for matrix degradation processes in diseases, such as chronic obstructive pulmonary disease, emphysema [13,14], and tumor progression [15], has been of great interest over the last three decades. Various methods for the identification and quantification of DES and IDES in body fluids have been reported (reviewed in [16]).…”

Section: Introductionmentioning

confidence: 99%

Fingerprinting Desmosine-Containing Elastin Peptides

Schräder

Heinz

Majovsky

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. 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 C x H y N, 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.

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Progress in the methodological strategies for the detection in real samples of desmosine and isodesmosine, two biological markers of elastin degradation

Cited by 28 publications

References 91 publications

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

Micellar Electrokinetic Chromatography with Laser Induced Detection and liquid chromatography tandem mass-spectrometry-based desmosine assays in urine of patients with Chronic Obstructive Pulmonary Disease: A comparative analysis

Fingerprinting Desmosine-Containing Elastin Peptides

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