F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome
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...
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Published in | Journal of lipid research Vol. 52; no. 12; pp. 2287 - 2297 |
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Main Authors | , , , , , , , , , , , , , |
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 | |
Online Access | Get full text |
ISSN | 0022-2275 1539-7262 1539-7262 |
DOI | 10.1194/jlr.P017798 |
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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 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 |
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AbstractList | 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 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.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. 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. 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 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. These data indicate for the fi rst time that quantifi cation 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 |
Author | Hayek, Joussef Ciccoli, Lucia Oger, Camille Bultel-Poncé, Valérie Leoncini, Silvia D'Esposito, Maurizio De Felice, Claudio Guy, Alexandre Galano, Jean-Marie Filosa, Stefania Durand, Thierry Valacchi, Giuseppe Signorini, Cinzia Pecorelli, Alessandra |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21917727$$D View this record in MEDLINE/PubMed https://hal.science/hal-00744233$$DView record in HAL |
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Keywords | myelin damage adrenic acid autism spectrum disorders methyl-CpG binding protein 2 |
Language | English |
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PublicationTitleAlternate | J Lipid Res |
PublicationYear | 2011 |
Publisher | Elsevier Inc American Society for Biochemistry and Molecular Biology The American Society for Biochemistry and Molecular Biology Elsevier |
Publisher_xml | – name: Elsevier Inc – name: American Society for Biochemistry and Molecular Biology – name: The American Society for Biochemistry and Molecular Biology – name: Elsevier |
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Snippet | 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... 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-... |
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SubjectTerms | 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 |
Title | F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome |
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