Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells

M. F. Lombardo, M. R. Ciriolo, G. Rotilio, L. Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.

Original languageEnglish
Pages (from-to)1733-1743
Number of pages11
JournalCellular and Molecular Life Sciences
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

Keywords

  • Antioxidant
  • Apoptosis
  • Copper depletion
  • Mitochondria
  • Neuroblastoma
  • Neurodegeneration
  • Oxidativestress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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