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In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehens...

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Autores principales: Altomare, Alessandra, Baron, Giovanna, Balbinot, Marta, Pedretti, Alessandro, Zoanni, Beatrice, Brioschi, Maura, Agostoni, Piergiuseppe, Carini, Marina, Banfi, Cristina, Aldini, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997412/
https://www.ncbi.nlm.nih.gov/pubmed/33673523
http://dx.doi.org/10.3390/antiox10030358
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author Altomare, Alessandra
Baron, Giovanna
Balbinot, Marta
Pedretti, Alessandro
Zoanni, Beatrice
Brioschi, Maura
Agostoni, Piergiuseppe
Carini, Marina
Banfi, Cristina
Aldini, Giancarlo
author_facet Altomare, Alessandra
Baron, Giovanna
Balbinot, Marta
Pedretti, Alessandro
Zoanni, Beatrice
Brioschi, Maura
Agostoni, Piergiuseppe
Carini, Marina
Banfi, Cristina
Aldini, Giancarlo
author_sort Altomare, Alessandra
collection PubMed
description Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry.
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spelling pubmed-79974122021-03-27 In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies Altomare, Alessandra Baron, Giovanna Balbinot, Marta Pedretti, Alessandro Zoanni, Beatrice Brioschi, Maura Agostoni, Piergiuseppe Carini, Marina Banfi, Cristina Aldini, Giancarlo Antioxidants (Basel) Article Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry. MDPI 2021-02-27 /pmc/articles/PMC7997412/ /pubmed/33673523 http://dx.doi.org/10.3390/antiox10030358 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Altomare, Alessandra
Baron, Giovanna
Balbinot, Marta
Pedretti, Alessandro
Zoanni, Beatrice
Brioschi, Maura
Agostoni, Piergiuseppe
Carini, Marina
Banfi, Cristina
Aldini, Giancarlo
In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title_full In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title_fullStr In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title_full_unstemmed In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title_short In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies
title_sort in-depth age and ale profiling of human albumin in heart failure: ex vivo studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997412/
https://www.ncbi.nlm.nih.gov/pubmed/33673523
http://dx.doi.org/10.3390/antiox10030358
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