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

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.
AuthorsClaudio 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
JournalJournal of lipid research (J Lipid Res) Vol. 52 Issue 12 Pg. 2287-2297 (Dec 2011) ISSN: 1539-7262 [Electronic] United States
PMID21917727 (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

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