Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo

NEUROBIOLOGY OF DISEASE

卷:34

Article

Son, Marjatta¹  Fu, Qiao¹  Puttaparthi, Krishna¹  Matthews, Christina M.¹  Elliott, Jeffrey L.¹ 

[1] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA

关键词: Amyotrophic lateral sclerosis;    Mitochondria;    Cytochrome c oxidase;    Transgenic;    Motor neuron;    Paralysis;   

DOI  :  10.1016/j.nbd.2009.01.005

来源: Elsevier

【 摘 要 】

Over-expression of CCS in G93A SOD1 mice accelerates neurological disease and enhances mitochondrial pathology. We studied the effect of CCS over-expression in transgenic mice expressing G37P, G86R or L126Z SOD1 mutations in order to understand factors which influence mitochondrial dysfunction. Over-expression of CCS markedly decreased survival and produced mitochondrial vacuolation in G37R SOD1 mice but not in G86R or L126Z SOD1 mice. Moreover, CCS/G37R SOD1 spinal cord showed specific reductions in mitochondrial complex IV subunits consistent with an isolated COX deficiency, while no such reductions were detected in CCS/G86R or CCS/L126Z SOD1 mice. CCS over-expression increased the ratio of reduced to oxidized SOD1 monomers in the spinal cords of G37R SOD1 as well as G93A SOD1 mice, but did not influence the redox state of G86R or L126Z SOD1 monomers. The effects of CCS on disease are SOD1 mutation dependent and correlate with SOD1 redox susceptibility. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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