Measurements of Desmosine and Isodesmosine by Mass Spectrometry in COPD

Ma, Shuren; Lin, Yong Y.; Turino, Gerard M.

doi:10.1378/chest.06-2251

Cited by 112 publications

(140 citation statements)

References 23 publications

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“…Because desmosine is unique to elastin in mammals (it is, however, found in avian and reptilian egg-shell membranes [26,27]), it can be used as a quantitative marker for insoluble elastin levels in tissues and cultured cells. Many methods have been employed for detection and quantification of desmosine, including HPLC [28][29][30][31][32][33], radioimmunoassay [27,[34][35][36][37], ELISA [38][39][40], capillary electrophoresis, [41] and mass spectrometry [42][43][44]. Of these techniques, only RIA and ELISA are applicable to high throughput analysis.…”

Section: Quantitation Of Desmosinementioning

confidence: 99%

Methods in elastic tissue biology: Elastin isolation and purification

Mecham

2008

Methods

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Elastin provides recoil to tissues subjected to repeated stretch, such as blood vessels and the lung. It is encoded by a single gene in mammals and is secreted as a 60-70 kDa monomer call tropoelastin. The functional form of the protein is that of a large, highly crosslinked polymer that organizes as sheets or fibers in the extracellular matrix. Purification of mature, crosslinked elastin is problematic because its insolubility precludes its isolation using standard wet-chemistry techniques. Instead, relatively harsh experimental approaches designed to remove non-elastin 'contaminates' are employed to generate an insoluble product that has the amino acid composition expected of elastin. Although soluble, tropoelastin also presents problems for isolation and purification. The protein's extreme stickiness and susceptibility to proteolysis requires careful attention during purification and in tropoelastin-based assays. This article describes the most common approaches for purification of insoluble elastin and tropoelastin. It also addresses key aspects of studying tropoelastin production in cultured cells, where elastin expression is highly dependent upon cell type, culture conditions, and passage number.

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Section: Quantitation Of Desmosinementioning

confidence: 99%

Methods in elastic tissue biology: Elastin isolation and purification

Mecham

2008

Methods

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“…12,13,15,16,30,31 Using a similar RIA, Starcher et al 31 found a wide range of urinary desmosine levels in patients with CF (75 to 325 pmol desmosine/mg creatinine) with a significant amount of day-to-day variation. Downey et al 32 found that higher levels of urinary desmosine were associated with a poorer outcome at 1 year in a CF population.…”

Section: Discussionmentioning

confidence: 99%

“…Although we do not report control specimens, previous publications have documented nondetectable levels of desmosine in the sputum of adults without lung disease. 12,13 During our analysis, we chose not to normalize sputum desmosine levels. Unlike BAL fluid, which requires normal saline solution for collection, expectorated sputum samples do not, negating the need to account for dilution.…”

Section: Discussionmentioning

confidence: 99%

“…In multiple cross-sectional analyses of small numbers of adult patients with COPD, sputum levels of desmosine were determined to be elevated compared with nonsmoking control subjects. [12][13][14] Desmosine is also excreted in the urine, and levels can be elevated in patients with CF. 15,16 No investigator, however, has examined sputum desmosine concentrations serially in a cohort of well-characterized patients with CF during pulmonary exacerbation.…”

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confidence: 99%

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Sputum Desmosine During Hospital Admission for Pulmonary Exacerbation in Cystic Fibrosis

Laguna

Wagner

Luckey

et al. 2009

Chest

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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.

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“…P. aeruginosa (Amitani et al, 1991;Azghani et al, 2014;Yoo et al, 2014) or pulmonary tuberculosis (Greenlee Bacterial chemotaxis towards products of elastin et al , 2007)]. In addition to releasing larger pieces of the polymer, the degradation of elastin generates two nonnatural amino acids, desmosine and isodesmosine (Afdhal et al, 1997;Albarbarawi et al, 2013;Boutin et al, 2009;Kaga et al, 2003;Laguna et al, 2009Laguna et al, , 2012Lamerz et al, 2013;Ma et al, 2003Ma et al, , 2007Ma et al, , 2011Ma et al, , 2013Miliotis et al, 2013;Ongay et al, 2014;Osakabe et al, 1999). Desmosine and isodesmosine are 1,2,3,5-and 1,3,4,5-tetrasubstituted pyridinium amino acids, respectively that serve as the crosslinking molecules that bind the polymeric chains in elastin into a three-dimensional network Thomas et al, 1963).…”

Section: Introductionmentioning

confidence: 99%

Elastin degradation product isodesmosine is a chemoattractant for Pseudomonas aeruginosa

Sampedro¹,

Kato²,

Hill³

2015

Microbiology

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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. INTRODUCTIONPseudomonas aeruginosais, an opportunistic human pathogen that can cause acute and chronic infections, e.g. skin (Andonova & Urumova, 2013), lung (Munder et al., 2011), eye (Zegans et al., 2012, cystic fibrosis airway (Bethesda, 2011), chronic obstructive pulmonary disease airway (Murphy et al., 2008) and atherogenesis (Turkay et al., 2004). P. aeruginosa can sense chemical gradients using a chemosensory pathway linked to flagella or pili (Sampedro et al., 2014). P. aeruginosa PAO1 has 26 putative methyl-accepting chemotaxis proteins (MCPs). Thirteen of its 26 MCP-like proteins have been functionally characterized. Ten MCPs have been shown to mediate a flagella-based positive chemotaxis response to malate (PA2652), oxygen (Aer and Aer-2), ethylene (TlpQ), chloroethylenes (McpA), amino acids and gamma aminobutyrate (GABA) (PctABC) and inorganic phosphate (CtpH and CtpL) (Alvarez-Ortega & Harwood, 2007;Hong et al., 2004;Kim et al., 2006Kim et al., , 2007 Rico-Jiménez et al., 2013;Shitashiro et al., 2005;Taguchi et al., 1997;Wu et al., 2000). The MCPs responsible for detecting the 20 natural L-amino acids in PAO1 are the paralogous PctA, PctB and PctC receptors (Kuroda et al., 1995;Taguchi et al., 1997). PctA recognizes and mediates the response to most of the natural L-amino acids, while PctB is primarily involved in mediating taxis to glutamine and PctC to histidine and proline. Only one natural amino acid has been investigated as a chemotactic stimulant for P. aeruginosa, the human neurotransmitter GABA (Rico-Jiménez et al., 2013). GABA was shown to generate a positive chemotactic response in the concentration range 0.01-1 mM GABA, similar to that of the 20 natural amino acids investigated previously.Elastin is an insoluble extracellular matrix protein that provides elasticity to tissues and organs (Debelle & Tamburro, 1999;Mithieux & Weiss, 2005;Rosenbloom et al., 1993).This stretchy, flexible protein is en...

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Measurements of Desmosine and Isodesmosine by Mass Spectrometry in COPD

Cited by 112 publications

References 23 publications

Methods in elastic tissue biology: Elastin isolation and purification

Methods in elastic tissue biology: Elastin isolation and purification

Sputum Desmosine During Hospital Admission for Pulmonary Exacerbation in Cystic Fibrosis

Elastin degradation product isodesmosine is a chemoattractant for Pseudomonas aeruginosa

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