Amyloid β peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation

J. Xu, S. Chen, G. Ku, S. H. Ahmed, J. Xu, H. Chen, C. Y. Hsu

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Amyloid β peptide (Aβ), a 39 to 43 amino acid fragment of the β-amyloid precursor protein (βAPP), forms insoluble fibrillar accumulation in neurofibrillary tangles and vascular plaques. Aβ has been implicated in neuronal and vascular degeneration in brain regions susceptible to plaque formation because of its cytotoxic effect on neurons and endothelial cells (ECs). The authors used a murine cerebral endothelial cell (CEC) line and primary cultures of bovine CECs to explore the cytotoxic mechanism of Aβ. Aβ 1-40 and Aβ 25-35 peptides caused cell death in a dose-dependent and time-dependent manner. Exposure to either Aβ 25-35 or Aβ 1-40 at 10 μmol/L for 48 hours caused at least 40% cell death. Cerebral endothelial cell death was characterized by nuclear condensation, mitochondrial dysfunction, and nuclear and mitochondrial DNA damage. Aβ 25-35 activated both caspase-8 and caspase-3 in murine CECs. zVAD-fmk, a broad-spectrum caspase inhibitor, prevented Aβ 25-35-induced increase in caspase-3 activity and CEC death. N-acetyl-cysteine, an antioxidant, also prevented Aβ-induced cell death. Together, these findings indicate that Aβ-mediated CEC death is an apoptotic process that is characterized by increased oxidative stress, caspase activation, mitochondrial dysfunction, and nuclear and mitochondrial DNA damage.

Original languageEnglish (US)
Pages (from-to)702-710
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Cell death
  • Mitochondrial DNA
  • Oxidative stress

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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