Seleno-L-methionine protects against β-amyloid and iron/hydrogen peroxide-mediated neuron death

Shuling Xiong, William R. Markesbery, Changxing Shao, Mark A. Lovell

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Increasing evidence suggests a role for oxidative stress in several neurodegenerative diseases, including Alzheimer's disease (AD), and that selenium compounds may function as antioxidants. To evaluate the antioxidant mechanism of selenium, primary rat hippocampal neurons were pretreated with seleno-L-methionine (SeMet) for 16 h prior to treatment with iron/hydrogen peroxide (Fe2+/H2O2) or amyloid beta peptide (Aβ25-35); free radical generation was assessed using laser confocal microscopy and CM-H2DCFDA and APF. Treatment with Fe 2+/H2O2 or Aβ significantly decreased cell survival and increased free radical generation compared to cultures treated with vehicle alone. In contrast, cultures pretreated with SeMet showed significantly (p < 0.05) increased survival and significantly lower CM-H 2DCFDA and APF fluorescence compared to Fe2+/H 2O2 or Aβ treated cultures. To determine if SeMet protection was mediated by glutathione peroxidase (GPx), levels of GPx protein and activity were measured using confocal microscopy and a selenium-dependent GPx specific antibody and an activity assay. Pretreatment with SeMet significantly (p < 0.05) increased GPx protein and activity in Fe 2+/H2O2- and Aβ-treated cultures compared to cultures treated with Fe2+/H2O2 or Aβ alone. These data suggest that SeMet can decrease free radical generation induced by Fe2+/H2O2 or Aβ through modulation of GPx and may be suitable as a potential therapeutic agent in neurodegenerative diseases where there is increased oxidative stress.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalAntioxidants and Redox Signaling
Volume9
Issue number4
DOIs
StatePublished - Apr 2007

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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