Oxidative damage has been reported in Rett syndrome (RTT), a pervasive development disorder mainly caused in up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. Herein, we have synthesized F2-dihomo-isoprostanes (F2-dihomo-IsoPs), peroxidation products from adrenic acid (AdA, 22:4 n-6), a known component of myelin, and tested the potential value of F2-dihomo-IsoPs as a novel disease marker and its relationship with clinical presentation, and disease progression. F2-dihomo-IsoPs were determined by a gas chromatography/negative ion chemical ionization tandem mass spectrometry. Newly synthetized F2-dihomo-IsoP isomers (ent-7(RS)-F2t-dihomo-IsoP and 17-F2t-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)-F2t-dihomo-IsoP and 17-F2t-dihomo-IsoP. Average plasma F2-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 F2-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.

F2-Dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome.

Pecorelli A.;VALACCHI, Giuseppe;
2011

Abstract

Oxidative damage has been reported in Rett syndrome (RTT), a pervasive development disorder mainly caused in up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. Herein, we have synthesized F2-dihomo-isoprostanes (F2-dihomo-IsoPs), peroxidation products from adrenic acid (AdA, 22:4 n-6), a known component of myelin, and tested the potential value of F2-dihomo-IsoPs as a novel disease marker and its relationship with clinical presentation, and disease progression. F2-dihomo-IsoPs were determined by a gas chromatography/negative ion chemical ionization tandem mass spectrometry. Newly synthetized F2-dihomo-IsoP isomers (ent-7(RS)-F2t-dihomo-IsoP and 17-F2t-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)-F2t-dihomo-IsoP and 17-F2t-dihomo-IsoP. Average plasma F2-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 F2-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.
De Felice, C.; Signorini, C.; Durand, T.; Oger, C.; Guy, A.; Bultel Ponce, V.; Galano, J. M.; Ciccoli, L.; Leoncini, S.; D'Esposito, M.; Filosa, S.; Pecorelli, A.; Valacchi, Giuseppe; Hayek, J.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1516321
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