title: 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.
authors.affiliation: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy. Electronic address: geniente@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Department of Pathophysiology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - UM I - UM II, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - UM I - UM II, Montpellier, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - UM I - UM II, Montpellier, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guy
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - UM I - UM II, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bultel-Poncé
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS - UM I - UM II, Montpellier, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.affiliation: Department of Pathophysiology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.affiliation: Department of Pathophysiology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso," CNR, Napoli, Italy; Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso," CNR, Napoli, Italy; Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.affiliation: Department of Pathophysiology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.affiliation: Department of Food and Nutrition, Kyung Hee University, Seoul, Korea; Department of Evolutionary Biology, University of Ferrara, Ferrara, Italy; and.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004883:Erucic Acids / Q000378:metabolism; D028441:F2-Isoprostanes / Q000097:blood* / Q000737:chemistry; D005231:Fatty Acids, Unsaturated; D005260:Female; D006801:Humans; D007223:Infant; D015227:Lipid Peroxidation; D009186:Myelin Sheath / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress; D015518:Rett Syndrome / Q000097:blood* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004883:Erucic Acids; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; C011395:adrenic acid