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β Amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH

journal contribution
posted on 2023-05-17, 02:28 authored by Klug, GM, Losic, D, Subasinghe, SS, Aguilar, MI, Martin, LL, David SmallDavid Small
Amyloid protein (Aâ1-40) aggregation and conformation was examined using native and sodium dodecyl sulfate/ polyacrylamide gel electrophoresis, and the results compared with those obtained by atomic force microscopy, and with Congo red binding, sedimentation and turbidity assays. The amount of Aâ aggregation measured was different, depending upon the method used. Incubation for 15 min at pH 5.0 or in the presence of Fe2+, Cu 2+ or Zn2+ did not alter the level of Aâ oligomers observed on SDS and native gels. However, the slow aggregation of Aâ to form high molecular mass species over 5 days was inhibited. In contrast, when Aâ aggregation was monitored using a Congo red binding assay or sedimentation assay, a rapid increase in Aâ aggregation was observed after incubation for 15 min at pH 5.0, or in the presence of Fe2+, Cu 2+ or Zn2+. The low pH-, Zn2+- or Cu 2+-induced Aâ aggregation measured in a turbidity assay was reversible. In contrast, a considerable proportion of the Aâ aggregation measured by native and SDS/PAGE was stable. Atomic force microscopy studies showed that Aâ aged at pH 5.0 or in the presence of Zn2+ produced larger looser rod-shaped aggregates than at pH 7.4. Aâ that had been aged at pH 7.4 was more cytotoxic than Aâ aged at pH 5.0. Taken together, the results suggest that Aâ oligomerizes via two mutually exclusive mechanisms to form two different types of aggregates, which differ in their cytotoxic properties.

History

Publication title

The FEBS Journal

Volume

270

Issue

21

Pagination

4282-4293

ISSN

1742-464X

Department/School

Menzies Institute for Medical Research

Publisher

Wiley-Blackwell Publishing Ltd.

Place of publication

United Kingdom

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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