Abstract |
Oxidative damage has been reported in Rett syndrome (RTT), a pervasive development disorder mainly caused up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. We have recently synthesized F(2)-Dihomo-isoprostanes (F(2)-Dihomo-IsoP), peroxidation products from adrenic acid (C22:4 n - 6, AdA), a known component of myelin, and tested the potential value of F(2)-Dihomo-IsoPs as a novel disease marker and its relationship with clinical presentation, and disease progression. F(2)-Dihomo-IsoPs were determined by a gas chromatography/negative ion chemical ionization tandem mass spectrometry. The ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP were used as reference standards. The measured ions were the product ions at m/z 327 derived from the [M - 181](-) precursor ions (m/z 597) produced from both the derivatized ent-7(RS)-F(2t)-Dihomo-IsoP and 17-F(2t)-Dihomo-IsoP. Average plasma F(2)-Dihomo-IsoP levels in RTT were about 1 order of magnitude higher than in healthy controls, being higher in typical RTT as compared to RTT variants, with a remarkable increase of about 2 orders of magnitude in patients at the earliest stage of the disease followed by a steady decrease during the natural clinical progression. These data indicate for the first time that quantification of F(2)-Dihomo-IsoPs in plasma represents an early marker of the disease and may provide a better understanding of the pathogenic mechanisms behind the neurological regression in patients with RTT.
|
Authors | Thierry Durand, Claudio De Felice, Cinzia Signorini, Camille Oger, Valérie Bultel-Poncé, Alexandre Guy, Jean-Marie Galano, Silvia Leoncini, Lucia Ciccoli, Alessandra Pecorelli, Giuseppe Valacchi, Joussef Hayek |
Journal | Biochimie
(Biochimie)
Vol. 95
Issue 1
Pg. 86-90
(Jan 2013)
ISSN: 1638-6183 [Electronic] France |
PMID | 23009927
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
Copyright | Copyright © 2012 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Biomarkers
- Erucic Acids
- F2-Isoprostanes
- Fatty Acids, Unsaturated
- MECP2 protein, human
- Methyl-CpG-Binding Protein 2
- adrenic acid
|
Topics |
- Biomarkers
(blood)
- Brain
(drug effects, metabolism, pathology)
- Erucic Acids
(chemistry, metabolism)
- F2-Isoprostanes
(administration & dosage, blood, chemical synthesis, pharmacokinetics)
- Fatty Acids, Unsaturated
- Humans
- Leukoencephalopathies
(drug therapy, metabolism, pathology)
- Lipid Peroxidation
(drug effects)
- Methyl-CpG-Binding Protein 2
(genetics, metabolism)
- Myelin Sheath
(chemistry, pathology)
- Oxidative Stress
- Rett Syndrome
(blood, diagnosis, pathology)
|