Protein succination as a potential surrogate biomarker of airway obstruction. The ilervas project. (October 2020)

• Record Type: Journal Article
• Authors: González, J.; Gracia-Lavedan, E.; Pamplona, R.; Fernández, E.; Lecube, A.; de-Torres, J.P.; Barbé, F.; Torres, G.; Benabdelhak, Ikram; Bermúdez, Marcelino; Castro, Eva; de Batlle, Jordi; Colàs-Campàs, Laura; Hernández, Marta; Jové, Mariano; Miquel, Eva; Martínez, Montserrat
• Is Part Of: Respiratory medicine. Volume 172(2020)
• Publication Date: 2020-10
• Subjects: Advanced glycation end-products -- S-(2-succino) cysteine -- Skin autofluorescence -- Systemic inflammation -- Oxidative stress -- Mitochondrial metabolic stress; AGEs Advanced Glycation End-products -- CEL Carboxyethyl-lysine -- CI Confidence Interval -- CMC Carboxymethyl-cysteine -- CML Carboxymethyl-lysine -- AO Airway Obstruction -- OR Odds Ratio -- SAF Skin Autofluorescence -- 2SC S-(2-succino)cysteine; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2020.106124
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: Background: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. The latter can alter metabolite intermediates in the Krebs cycle leading to the formation of the cysteine-fumarate adduct S -(2-succino) cysteine (2SC) in proteins (protein succination). Protein succination has not been described in airways diseases. Research question: To assess differences in levels of AGEs and 2SC between patients with AO and normal spirometry. Study design: and Methods: In this case-control study, we investigated 35 moderate to severe AO patients and 31 subjects with normal spirometry, matched for age, gender, body mass index (BMI), tobacco history, prediabetes and adherence to Mediterranean diet. Plasma 2SC and AGEs concentrations were measured by GS/MS, and AGEs in skin were determined measuring autofluorescence (SAF). Multivariate logistic regression models explored the association between AGEs in the skin, 2SC and the presence of AO. Results: The population was predominantly middle-age (mean of 58.7 years-old), overweight (median of BMI 26.7 kg/m 2 ) and male subjects (69.7%). Patients with AO showed higher values of SAF ( p = 0.04 ) and 2SC ( p = 0.047). No differences were observed for plasma AGEs. SAF and 2SC were significantly associated with the presence of AO after adjusting for age, gender, smoking history, BMI and Mediterranean diet score ( p = 0.041 and p = 0.038, respectively). Interpretation: Skin AGEs and 2SC are increased in patients with moderate to severe AO and independently associated with its presence. Further studies should confirm these findings and explore their potential role as a biomarker for the disease. Highlights: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. This leads the formation of the cysteine-fumarate adduct S -(2-succino) cysteine (2SC) in proteins (protein succination). S -(2-succino) cysteine (2SC) levels and AGE skin levels are increased in moderate to severe AO patients. These molecules have a potential role as biomarkers for AO.