eCite Digital Repository

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

Citation

Klug, GM and Losic, D and Subasinghe, SS and Aguilar, MI and Martin, LL and Small, DH, β Amyloid protein oligomers induced by metal ions and acid pH are distinct from those generated by slow spontaneous ageing at neutral pH, The FEBS Journal, 270, (21) pp. 4282-4293. ISSN 1742-464X (2003) [Refereed Article]

DOI: doi:10.1046/j.1432-1033.2003.03815.x

Abstract

Amyloid protein (A1-40) 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 A 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 A oligomers observed on SDS and native gels. However, the slow aggregation of A to form high molecular mass species over 5 days was inhibited. In contrast, when A aggregation was monitored using a Congo red binding assay or sedimentation assay, a rapid increase in A 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 A aggregation measured in a turbidity assay was reversible. In contrast, a considerable proportion of the A aggregation measured by native and SDS/PAGE was stable. Atomic force microscopy studies showed that A aged at pH 5.0 or in the presence of Zn2+ produced larger looser rod-shaped aggregates than at pH 7.4. A that had been aged at pH 7.4 was more cytotoxic than A aged at pH 5.0. Taken together, the results suggest that A oligomerizes via two mutually exclusive mechanisms to form two different types of aggregates, which differ in their cytotoxic properties.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:63311
Year Published:2003
Web of Science® Times Cited:78
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-04-28
Last Modified:2010-09-16
Downloads:0

Repository Staff Only: item control page