title: Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich's Ataxia Transgenic Mice.
abstract: Friedreich's ataxia (FA) is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF), which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXN)YG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse) exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold) and heart (1.2-fold). LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. luciacalatrava@gmail.com.
authors.forename: Lucía
authors.initials: L
authors.lastname: Calatrava-Ferreras
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. rgonzalo-ibis@us.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gonzalo-Gobernado
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. diana.reimers@hrc.es.
authors.forename: Diana
authors.initials: D
authors.lastname: Reimers
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. antonio.sanchez@hrc.es.
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Herranz
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. m.jose.casarejos@hrc.es.
authors.forename: María J
authors.initials: MJ
authors.lastname: Casarejos
authors.affiliation: Service of Neurology, Ramón y Cajal Hospital, 28034 Madrid, Spain. jimeneze@yahoo.com.
authors.forename: Adriano
authors.initials: A
authors.lastname: Jiménez-Escrig
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia Facultad de Medicina Universidad Autónoma de Madrid, 28400 Madrid, Spain. javier.regadera@uam.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Regadera
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia Facultad de Medicina Universidad Autónoma de Madrid, 28400 Madrid, Spain. juan.velascomartin@uam.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Velasco-Martín
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. manuela.vmqm@gmail.com.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vallejo-Muñoz
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. luciacalatrava@gmail.com.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Díaz-Gil
authors.affiliation: Service of Neurobiology, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain. eulalia.bazan@hrc.es.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Bazán
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000627:therapeutic use*; D015153:Blotting, Western; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007150:Immunohistochemistry; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D012709:Serum Albumin / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D000096923:Frataxin
chemical_list: D001663:Bilirubin; D005978:Glutathione; D033862:Iron-Binding Proteins; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D000096923:Frataxin; C053498:albumin-bilirubin complex
keywords: Friedreich’s ataxia; frataxin; liver growth factor; neuroprotection; oxidative stress