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N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity

In the present paper, the extracellular antioxidant activity of N-acetyl-cysteine (NAC) is explained by considering its ability to regenerate the free form of albumin Cys34 by breaking the disulfide bond of the cysteinylated form (HSA-Cys). NAC’s capability to regenerate albumin Cys34 (HSA-SH) was s...

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Autores principales: Altomare, Alessandra, Baron, Giovanna, Brioschi, Maura, Longoni, Martina, Butti, Riccardo, Valvassori, Edoardo, Tremoli, Elena, Carini, Marina, Agostoni, Piergiuseppe, Vistoli, Giulio, Banfi, Cristina, Aldini, Giancarlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278672/
https://www.ncbi.nlm.nih.gov/pubmed/32354002
http://dx.doi.org/10.3390/antiox9050367
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author Altomare, Alessandra
Baron, Giovanna
Brioschi, Maura
Longoni, Martina
Butti, Riccardo
Valvassori, Edoardo
Tremoli, Elena
Carini, Marina
Agostoni, Piergiuseppe
Vistoli, Giulio
Banfi, Cristina
Aldini, Giancarlo
author_facet Altomare, Alessandra
Baron, Giovanna
Brioschi, Maura
Longoni, Martina
Butti, Riccardo
Valvassori, Edoardo
Tremoli, Elena
Carini, Marina
Agostoni, Piergiuseppe
Vistoli, Giulio
Banfi, Cristina
Aldini, Giancarlo
author_sort Altomare, Alessandra
collection PubMed
description In the present paper, the extracellular antioxidant activity of N-acetyl-cysteine (NAC) is explained by considering its ability to regenerate the free form of albumin Cys34 by breaking the disulfide bond of the cysteinylated form (HSA-Cys). NAC’s capability to regenerate albumin Cys34 (HSA-SH) was studied by MS intact protein analysis in human plasma and in a concentration range of NAC easily achievable after oral and i.v. administration (5–50 µg/mL). NAC dose-dependently broke the HSA-Cys bond to form the dimer NAC-Cys thus regenerating Cys34, whose reduced state was maintained for at least 120 min. Cys was faster in restoring Cys34, according to the reaction constant determined with the glutathione disulfide (GSSG) reaction, but after 60 min the mixed disulfide HSA-Cys turned back due to the reaction of the dimer Cys-Cys with Cys34. The explanation for the different rate exchanges between Cys-Cys and Cys-NAC with Cys34 was given by molecular modeling studies. Finally, the Cys34 regenerating effect of NAC was related to its ability to improve the total antioxidant capacity of plasma (TRAP assay). The results well indicate that NAC greatly increases the plasma antioxidant activity and this effect is not reached by a direct effect but through the regenerating effect of Cys34.
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spelling pubmed-72786722020-06-12 N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity Altomare, Alessandra Baron, Giovanna Brioschi, Maura Longoni, Martina Butti, Riccardo Valvassori, Edoardo Tremoli, Elena Carini, Marina Agostoni, Piergiuseppe Vistoli, Giulio Banfi, Cristina Aldini, Giancarlo Antioxidants (Basel) Article In the present paper, the extracellular antioxidant activity of N-acetyl-cysteine (NAC) is explained by considering its ability to regenerate the free form of albumin Cys34 by breaking the disulfide bond of the cysteinylated form (HSA-Cys). NAC’s capability to regenerate albumin Cys34 (HSA-SH) was studied by MS intact protein analysis in human plasma and in a concentration range of NAC easily achievable after oral and i.v. administration (5–50 µg/mL). NAC dose-dependently broke the HSA-Cys bond to form the dimer NAC-Cys thus regenerating Cys34, whose reduced state was maintained for at least 120 min. Cys was faster in restoring Cys34, according to the reaction constant determined with the glutathione disulfide (GSSG) reaction, but after 60 min the mixed disulfide HSA-Cys turned back due to the reaction of the dimer Cys-Cys with Cys34. The explanation for the different rate exchanges between Cys-Cys and Cys-NAC with Cys34 was given by molecular modeling studies. Finally, the Cys34 regenerating effect of NAC was related to its ability to improve the total antioxidant capacity of plasma (TRAP assay). The results well indicate that NAC greatly increases the plasma antioxidant activity and this effect is not reached by a direct effect but through the regenerating effect of Cys34. MDPI 2020-04-28 /pmc/articles/PMC7278672/ /pubmed/32354002 http://dx.doi.org/10.3390/antiox9050367 Text en © 2020 by the authors. 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/).
spellingShingle Article
Altomare, Alessandra
Baron, Giovanna
Brioschi, Maura
Longoni, Martina
Butti, Riccardo
Valvassori, Edoardo
Tremoli, Elena
Carini, Marina
Agostoni, Piergiuseppe
Vistoli, Giulio
Banfi, Cristina
Aldini, Giancarlo
N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title_full N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title_fullStr N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title_full_unstemmed N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title_short N-Acetyl-Cysteine Regenerates Albumin Cys34 by a Thiol-Disulfide Breaking Mechanism: An Explanation of Its Extracellular Antioxidant Activity
title_sort n-acetyl-cysteine regenerates albumin cys34 by a thiol-disulfide breaking mechanism: an explanation of its extracellular antioxidant activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278672/
https://www.ncbi.nlm.nih.gov/pubmed/32354002
http://dx.doi.org/10.3390/antiox9050367
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