Aβ(25-35) peptide displays H2O2-like reactivity towards aqueous FE2+, nitroxide spin probes, Ant) synaptosomal membrane proteins

D. Allan Butterfield, Laura Martin, John M. Carney, Kenneth Hensley

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Amyloid beta peptides (Aβs) are found in abnormally high accumulations in brains of persons with Alzheimer's disease, and are believed to contribute to cognitive decline in this disorder. Synthetic Aβ and its peptide fragment 25-35 [Aβ(25-35)] are toxic to cells in culture; however, the exact mechanism of amyloid peptide toxicity is not known. An emerging hypothesis contends that Aβ toxicity results from peptide-mediated free radical reactions and generation of reactive oxygen species [Hensley, et al., Proc. Natl. Acad. Sci. USA 19: 3270-3274 (1994); Harris, et al., Exp. Neurol. 131: 193-202 (1995)]. Recently, we reported that reactivity of Aβ toward the oxidation-sensitive enzyme glutamine synthetase is related to the peptide's reactivity toward the spin trap phenyl-tert-butyl nitrone (PBN) [Hensley, et al., Neuroreport 6: 489-492 (1995)]. Neuronal damage may be due, in part, to oxidative processes initiated by amyloid-derived free radicals species. This work presents evidence from electron paramagnetic resonance (EPR) spin labeling techniques and spectrophotometric assays that a portion of synthetic Aβ(25-35) demonstrates hydrogen peroxide-like reactivity toward Fe2+, nitroxide spin probes, and neocortical synaptasomal membrane proteins. These results are discussed with reference to free radical membrane damage and neurotoxicity in Alzheimer's disease.

Original languageEnglish
Pages (from-to)217-228
Number of pages12
JournalLife Sciences
Volume58
Issue number3
DOIs
StatePublished - Dec 8 1995

Bibliographical note

Funding Information:
This work was supported in part by grants from NIH (AG-10836). K. Hensley is an Office of Naval Research Pre-Doctoral Fellow.

Keywords

  • amyloid
  • free radicals
  • nitroxides
  • protein oxidation
  • spin labels

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology

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