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

• Published in: Journal of lipid research Vol. 52; no. 12; pp. 2287 - 2297
• Main Authors: De Felice, Claudio, Signorini, Cinzia, Durand, Thierry, Oger, Camille, Guy, Alexandre, Bultel-Poncé, Valérie, Galano, Jean-Marie, Ciccoli, Lucia, Leoncini, Silvia, D'Esposito, Maurizio, Filosa, Stefania, Pecorelli, Alessandra, Valacchi, Giuseppe, Hayek, Joussef
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2011; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Adolescent; adrenic acid; Adult; autism spectrum disorders; Biomarkers - blood; Biomarkers - chemistry; Chemical Sciences; Child; Child, Preschool; Disease Progression; Endocrinology and metabolism; Erucic Acids - metabolism; F2-Isoprostanes - blood; F2-Isoprostanes - chemistry; Fatty Acids, Unsaturated; Female; Human health and pathology; Humans; Infant; Life Sciences; Lipid Peroxidation; Medicinal Chemistry; methyl-CpG binding protein 2; myelin damage; Myelin Sheath - metabolism; Organ Specificity; Oxidative Stress; Patient-Oriented and Epidemiological Research; Rett Syndrome - blood; Rett Syndrome - metabolism; Young Adult; myelin damage; adrenic acid; autism spectrum disorders; methyl-CpG binding protein 2
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.P017798

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 F2-dihomo-isoprostanes (F2-dihomo-IsoPs), peroxidation products from adrenic acid (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 gas chromatography/negative-ion chemical ionization tandem mass spectrometry. Newly synthesized 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 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 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