Copper depletion increases the mitochondrial-associated SOD1 in neuronal cells

Mario Arciello, Concetta Rosa Capo, Sara D. Annibale, Mauro Cozzolino, Alberto Ferri, Maria Teresa Carri, Luisa Rossi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The role of copper in the toxicity of mutant copper-dependent enzyme superoxide dismutase (SOD1) found in patients affected with the familial form of amyotrophic lateral sclerosis (fALS) is widely debated. Here we report that treatment of human neuroblastoma cells SH-SY5Y with a specific copper chelator, triethylene tetramine (Trien) induces the decrease of intracellular copper level, paralleled by decreased activity of SOD1. A comparable effect is observed in mouse NSC-34-derived cells, a motoneuronal model, transfected for the inducible expression of either wild-type or G93A mutant human SOD1, one of the mutations associated with fALS. In both cell types, the drop of SOD1 activity is not paralleled by the same extent of decrease in SOD1 protein content. This discrepancy can be explained by the occurrence of a fraction of copper-free SOD1 upon copper depletion, which is demonstrated by the partial recovery of the enzyme activity after the addition of copper sulphate to homogenates of SH-SY5Y cells. Furthermore, copper depletion produces the enrichment of the physiological mitochondrial fraction of SOD1 protein, in both cells models. However, increasing the fraction of mitochondrial, possibly copper-free, mutant human SOD1 does not further alter mitochondrial morphology in NSC-34-derived cells. Thus, copper deficiency is not a factor which may worsen mitochondrial damage, which is one of the earliest events in fALS associated with mutant SOD1.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalBioMetals
Volume24
Issue number2
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Copper
neurons
copper
mutants
tetramethylenedisulfotetramine
Amyotrophic Lateral Sclerosis
cells
Copper Sulfate
Proteins
copper sulfate
Enzyme activity
Enzymes
Chelating Agents
chelating agents
Neuroblastoma
Superoxide Dismutase
Toxicity
superoxide dismutase
protein content
enzyme activity

Keywords

  • ALS
  • Copper
  • Mitochondria
  • NSC-34
  • SH-SY5Y
  • SOD1

ASJC Scopus subject areas

  • Biomaterials
  • Metals and Alloys
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Copper depletion increases the mitochondrial-associated SOD1 in neuronal cells. / Arciello, Mario; Capo, Concetta Rosa; Annibale, Sara D.; Cozzolino, Mauro; Ferri, Alberto; Carri, Maria Teresa; Rossi, Luisa.

In: BioMetals, Vol. 24, No. 2, 04.2011, p. 269-278.

Research output: Contribution to journalArticle

Arciello, Mario ; Capo, Concetta Rosa ; Annibale, Sara D. ; Cozzolino, Mauro ; Ferri, Alberto ; Carri, Maria Teresa ; Rossi, Luisa. / Copper depletion increases the mitochondrial-associated SOD1 in neuronal cells. In: BioMetals. 2011 ; Vol. 24, No. 2. pp. 269-278.
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