Increased isoprostanoid levels in brain from murine model of Krabbe disease – Relevance of isoprostanes, dihomo-isoprostanes and neuroprostanes to disease severity
| Autor: | Giovanna Pannuzzo, Jetty Chung-Yung Lee, Silvia Leoncini, Joussef Hayek, Camille Oger, Alessio Cortelazzo, Adriana Carol Eleonora Graziano, Cinzia Signorini, Claudio De Felice, Venera Cardile, Thierry Durand, Jean-Marie Galano |
|---|---|
| Přispěvatelé: | Università degli Studi di Siena = University of Siena (UNISI), University of Catania [Italy], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Azienda Ospedaliera Universitaria Senese, The University of Hong Kong (HKU) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Heterozygote Docosahexaenoic Acids [SDV]Life Sciences [q-bio] Gene Expression Biology Isoprostanes Murine models medicine.disease_cause Biochemistry Severity of Illness Index Pathogenesis White matter 03 medical and health sciences Myelin Mice 0302 clinical medicine Adrenic acid Physiology (medical) Internal medicine medicine Animals Humans Neuroprostanes Gray Matter Leukodystrophy Homozygote medicine.disease White Matter 3. Good health Leukodystrophy Globoid Cell Oxidative stress Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Krabbe disease Docosahexaenoic acid Mutation Fatty Acids Unsaturated 030217 neurology & neurosurgery Galactosylceramidase |
| Zdroj: | Free Radical Biology and Medicine Free Radical Biology and Medicine, Elsevier, 2019, 139, pp.46-54. ⟨10.1016/j.freeradbiomed.2019.05.014⟩ |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2019.05.014⟩ |
| Popis: | International audience; Krabbe disease (KD) is a rare and devastating pediatric leukodystrophy caused by mutations in the galactocerebrosidase (GALC) gene. The disease leads to impaired myelin formation and extensive myelin damage in the brain. Oxidative stress is implicated in the pathogenesis of KD but insofar few information is available. The gray and white matter of the brain are rich in docosahexaenoic acid and adrenic acid respectively and under non-enzymatic oxidative stress, release isoprostanoids, i.e. F4-neuroprostanes (F4-NeuroPs) and F2-dihomo-isoprostanes (F2-dihomo-IsoPs). In this study, the formation of isoprostanoids in brain tissue was investigated in a well-established KD mouse model (twitcher) that recapitulates the human pathology. According to the genotype determinations, three groups of mice were selected: wild-type control mice (n = 13), heterozygotes mice (carriers of GALC mutations, n = 14) and homozygous twitcher mice (n = 13). Measurement of F2-dihomo-IsoP and F4-NeuroP levels were performed on whole brain tissue obtained at day 15 and day 35 of the life cycle. Brain isoprostanoid levels were significantly higher in the twitcher mice compared to the heterozygous and wild-type control mice. However, F2-dihomo-IsoP and F4-NeuroP levels did not differ in brain of day 15 compared to day 35 of the heterozygote mice. Interestingly, isoprostanoid levels were proportionally enhanced with disease severity (F2-dihomo-IsoPs, rho = 0.54; F4-NeuroPs, rho = 0.581; P values ≤ 0.05; n = 13). Our findings are the first to show the key role of polyunsaturated fatty acid oxidative damage to brain grey and white matter in the pathogenesis and progression of KD. This shed new insights on the biochemical indexes of KD progression, and potentially provide information for novel therapeutic targets. |
| Databáze: | OpenAIRE |
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