The relationship between the aggregational state of the amyloid-β peptides and free radical generation by the peptides

Akira Monji, Hideo Utsumi, Tadashi Ueda, Taiji Imoto, Ichiro Yoshida, Sadayuki Hashioka, Ken Ichiro Tashiro, Nobutada Tashiro

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

In the present study, we investigated whether or not the amyloid-β protein (Aβ) peptide itself spontaneously generates free radicals using electron spin resonance (ESR) spectroscopy while also monitoring the aggregational state of Aβ and Aβ-induced cytotoxicity. The present results demonstrated a four-line spectrum in the presence of both Aβ40 and Aβ42 with N-tert-butyl-α-phenylnitrone (PBN), but not in the presence of PBN alone in phosphate-buffered saline (PBS). The fact that the four-line spectrum obtained for the Aβ/PBN in PBS was completely abolished in the presence of the iron-chelating agent Desferal demonstrated the observed four-line spectrum to be iron-dependent. The present study also revealed that either Aβ40 or Aβ42 with PBN in phosphate buffer (PB) did not produce any definite four-line spectrum. Both a thioflavine-T (Th-T) fluorometric assay and circular dichroism (CD) spectroscopy showed the amyloid fibril formation of Aβ in PBS to be much higher than that of Aβ in PB. Moreover, Aβ-induced cytotoxicity assays showed Aβ incubated in PBS to be more cytotoxic than that incubated in PB. These results thus suggest that Aβ-associated free radical generation is strongly influenced by the aggregational state of the peptides.

Original languageEnglish
Pages (from-to)1425-1432
Number of pages8
JournalJournal of Neurochemistry
Volume77
Issue number6
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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