Overexpression of superoxide dismutase 1 protects against β-amyloid peptide toxicity: Effect of estrogen and copper chelators

Fulvio Celsi, Alberto Ferri, Arianna Casciati, Nadia D'Ambrosi, Giuseppe Rotilio, Alfredo Costa, Cinzia Volonté, Maria Teresa Carrì

Research output: Contribution to journalArticlepeer-review

Abstract

β-Amyloid peptides (Aβ) are major constituents of senile plaques in Alzheimer's disease (AD) brain and contribute to neurodegeneration, operating through activation of apoptotic pathways. It has been proposed that Aβ induces death by oxidative stress, possibly through the generation of peroxynitrite from superoxide and nitric oxide. Estrogen is thought to play a protective role against neurodegeneration through a variety of mechanisms including scavenging of reactive oxygen species (ROS). In this study, we have challenged with Aβ, either in the presence or in the absence of 17β-estradiol, differentiated human neuroblastoma SH-SY5Y cells (named line SH) and the same line overexpressing anti-oxidant enzyme superoxide dismutase 1 (SOD1; named line WT). We have observed that: (1) WT cells are less susceptible than SH cells to Aβ insult; (2) caspase-3, but not caspase-1, is involved in Aβ-induced apoptosis in this system; (3) estrogen protects both lines, without significantly affecting SOD activity; and (4) copper chelators prevent Aβ-induced toxicity. Our results further support the notion that anti-oxidant therapy might be beneficial in the treatment of AD by preventing activation of selected apoptotic pathways.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalNeurochemistry International
Volume44
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • 17β-Estradiol
  • Apoptosis
  • Copper
  • Reactive oxygen species
  • Superoxide dismutase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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