Abstract |
Oxidative damage has been reported in Rett syndrome (RTT), a pervasive developmental disorder caused in up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 gene. Herein, we have synthesized F(2)-dihomo-isoprostanes (F(2)-dihomo-IsoPs), peroxidation products from adrenic acid (22:4 n-6), 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 gas chromatography/negative-ion chemical ionization tandem mass spectrometry. Newly synthesized F(2)-dihomo-IsoP isomers [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 one order of magnitude higher than those in healthy controls, being higher in typical RTT as compared with RTT variants, with a remarkable increase of about two orders of magnitude in patients at the earliest stage of the disease followed by a steady decrease during the natural clinical progression. hese 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 | Claudio De Felice, Cinzia Signorini, Thierry Durand, Camille Oger, Alexandre Guy, Valérie Bultel-Poncé, Jean-Marie Galano, Lucia Ciccoli, Silvia Leoncini, Maurizio D'Esposito, Stefania Filosa, Alessandra Pecorelli, Giuseppe Valacchi, Joussef Hayek |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 52
Issue 12
Pg. 2287-2297
(Dec 2011)
ISSN: 1539-7262 [Electronic] United States |
PMID | 21917727
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Biomarkers
- Erucic Acids
- F2-Isoprostanes
- Fatty Acids, Unsaturated
- adrenic acid
|
Topics |
- Adolescent
- Adult
- Biomarkers
(blood, chemistry)
- Child
- Child, Preschool
- Disease Progression
- Erucic Acids
(metabolism)
- F2-Isoprostanes
(blood, chemistry)
- Fatty Acids, Unsaturated
- Female
- Humans
- Infant
- Lipid Peroxidation
- Myelin Sheath
(metabolism)
- Organ Specificity
- Oxidative Stress
- Rett Syndrome
(blood, metabolism)
- Young Adult
|