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Antiglycative Activity and RAGE Expression in Rett Syndrome

Rett syndrome (RTT) is a human neurodevelopmental disorder, whose pathogenesis has been linked to both oxidative stress and subclinical inflammatory status (OxInflammation). Methylglyoxal (MG), a glycolytic by-product with cytotoxic and pro-oxidant power, is the major precursor in vivo of advanced g...

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Autores principales: Cordone, Valeria, Pecorelli, Alessandra, Benedusi, Mascia, Santini, Silvano, Falone, Stefano, Hayek, Joussef, Amicarelli, Fernanda, Valacchi, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406506/
https://www.ncbi.nlm.nih.gov/pubmed/30781346
http://dx.doi.org/10.3390/cells8020161
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author Cordone, Valeria
Pecorelli, Alessandra
Benedusi, Mascia
Santini, Silvano
Falone, Stefano
Hayek, Joussef
Amicarelli, Fernanda
Valacchi, Giuseppe
author_facet Cordone, Valeria
Pecorelli, Alessandra
Benedusi, Mascia
Santini, Silvano
Falone, Stefano
Hayek, Joussef
Amicarelli, Fernanda
Valacchi, Giuseppe
author_sort Cordone, Valeria
collection PubMed
description Rett syndrome (RTT) is a human neurodevelopmental disorder, whose pathogenesis has been linked to both oxidative stress and subclinical inflammatory status (OxInflammation). Methylglyoxal (MG), a glycolytic by-product with cytotoxic and pro-oxidant power, is the major precursor in vivo of advanced glycation end products (AGEs), which are known to exert their detrimental effect via receptor- (e.g., RAGE) or non-receptor-mediated mechanisms in several neurological diseases. On this basis, we aimed to compare fibroblasts from healthy subjects (CTR) with fibroblasts from RTT patients (N = 6 per group), by evaluating gene/protein expression patterns, and enzymatic activities of glyoxalases (GLOs), along with the levels of MG-dependent damage in both basal and MG-challenged conditions. Our results revealed that RTT is linked to an alteration of the GLOs system (specifically, increased GLO2 activity), that ensures unchanged MG-dependent damage levels. However, RTT cells underwent more pronounced cell death upon exogenous MG-treatment, as compared to CTR, and displayed lower RAGE levels than CTR, with no alterations following MG-treatment, thus suggesting that an adaptive response to dicarbonyl stress may occur. In conclusion, besides OxInflammation, RTT is associated with reshaping of the major defense systems against dicarbonyl stress, along with an altered cellular stress response towards pro-glycating insults.
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spelling pubmed-64065062019-03-19 Antiglycative Activity and RAGE Expression in Rett Syndrome Cordone, Valeria Pecorelli, Alessandra Benedusi, Mascia Santini, Silvano Falone, Stefano Hayek, Joussef Amicarelli, Fernanda Valacchi, Giuseppe Cells Article Rett syndrome (RTT) is a human neurodevelopmental disorder, whose pathogenesis has been linked to both oxidative stress and subclinical inflammatory status (OxInflammation). Methylglyoxal (MG), a glycolytic by-product with cytotoxic and pro-oxidant power, is the major precursor in vivo of advanced glycation end products (AGEs), which are known to exert their detrimental effect via receptor- (e.g., RAGE) or non-receptor-mediated mechanisms in several neurological diseases. On this basis, we aimed to compare fibroblasts from healthy subjects (CTR) with fibroblasts from RTT patients (N = 6 per group), by evaluating gene/protein expression patterns, and enzymatic activities of glyoxalases (GLOs), along with the levels of MG-dependent damage in both basal and MG-challenged conditions. Our results revealed that RTT is linked to an alteration of the GLOs system (specifically, increased GLO2 activity), that ensures unchanged MG-dependent damage levels. However, RTT cells underwent more pronounced cell death upon exogenous MG-treatment, as compared to CTR, and displayed lower RAGE levels than CTR, with no alterations following MG-treatment, thus suggesting that an adaptive response to dicarbonyl stress may occur. In conclusion, besides OxInflammation, RTT is associated with reshaping of the major defense systems against dicarbonyl stress, along with an altered cellular stress response towards pro-glycating insults. MDPI 2019-02-15 /pmc/articles/PMC6406506/ /pubmed/30781346 http://dx.doi.org/10.3390/cells8020161 Text en © 2019 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
Cordone, Valeria
Pecorelli, Alessandra
Benedusi, Mascia
Santini, Silvano
Falone, Stefano
Hayek, Joussef
Amicarelli, Fernanda
Valacchi, Giuseppe
Antiglycative Activity and RAGE Expression in Rett Syndrome
title Antiglycative Activity and RAGE Expression in Rett Syndrome
title_full Antiglycative Activity and RAGE Expression in Rett Syndrome
title_fullStr Antiglycative Activity and RAGE Expression in Rett Syndrome
title_full_unstemmed Antiglycative Activity and RAGE Expression in Rett Syndrome
title_short Antiglycative Activity and RAGE Expression in Rett Syndrome
title_sort antiglycative activity and rage expression in rett syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406506/
https://www.ncbi.nlm.nih.gov/pubmed/30781346
http://dx.doi.org/10.3390/cells8020161
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