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

Marjatta Son, Qiao Fu, Krishna Puttaparthi, Christina M. Matthews, Jeffrey L. Elliott

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 G37R, 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.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalNeurobiology of Disease
Volume34
Issue number1
DOIs
StatePublished - Apr 2009

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Oxidation-Reduction
Spinal Cord
Mitochondrial Diseases
Mutation
Transgenic Mice
Pathology

Keywords

  • Amyotrophic lateral sclerosis
  • Cytochrome c oxidase
  • Mitochondria
  • Motor neuron
  • Paralysis
  • Transgenic

ASJC Scopus subject areas

  • Neurology

Cite this

Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo. / Son, Marjatta; Fu, Qiao; Puttaparthi, Krishna; Matthews, Christina M.; Elliott, Jeffrey L.

In: Neurobiology of Disease, Vol. 34, No. 1, 04.2009, p. 155-162.

Research output: Contribution to journalArticle

Son, Marjatta ; Fu, Qiao ; Puttaparthi, Krishna ; Matthews, Christina M. ; Elliott, Jeffrey L. / Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo. In: Neurobiology of Disease. 2009 ; Vol. 34, No. 1. pp. 155-162.
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