Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich's Ataxia Transgenic Mice

被引:6
作者
Calatrava-Ferreras, Lucia [1 ]
Gonzalo-Gobernado, Rafael [1 ]
Reimers, Diana [1 ]
Herranz, Antonio S. [1 ]
Casarejos, Maria J. [1 ]
Jimenez-Escrig, Adriano [2 ]
Regadera, Javier [3 ]
Velasco-Martin, Juan [3 ]
Vallejo-Munoz, Manuela [1 ]
Jose Diaz-Gil, Juan [1 ]
Bazan, Eulalia [1 ]
机构
[1] Ramon & Cajal Inst Hlth Res IRYCIS, Serv Neurobiol, Madrid 28034, Spain
[2] Hosp Ramon & Cajal, Serv Neurol, E-28034 Madrid, Spain
[3] Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid 28400, Spain
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2016年 / 17卷 / 12期
关键词
liver growth factor; Friedreich's ataxia; neuroprotection; oxidative stress; frataxin; NEURAL STEM-CELLS; GLUTATHIONE; DEFICIENCY; MODEL; BLOOD; RATS; IDENTIFICATION; PATHOGENESIS; ACTIVATION; INJECTION;
D O I
10.3390/ijms17122066
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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.
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页数:17
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