Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783401320994045952 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6406506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cordonevaleria antiglycativeactivityandrageexpressioninrettsyndrome AT pecorellialessandra antiglycativeactivityandrageexpressioninrettsyndrome AT benedusimascia antiglycativeactivityandrageexpressioninrettsyndrome AT santinisilvano antiglycativeactivityandrageexpressioninrettsyndrome AT falonestefano antiglycativeactivityandrageexpressioninrettsyndrome AT hayekjoussef antiglycativeactivityandrageexpressioninrettsyndrome AT amicarellifernanda antiglycativeactivityandrageexpressioninrettsyndrome AT valacchigiuseppe antiglycativeactivityandrageexpressioninrettsyndrome |