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Cell Biology International (2008) 32, 447455 (Printed in Great Britain)
β-Amyloid peptides 1–40βA and 25–35βA suppress human amylin-mediated death of RINm5F islet β-cells with distinct actions on fibril formation
Department of Physiology, School of Medical and Health Sciences, University of Auckland, Private Bag 9201, Auckland, New Zealand
Amyloid deposition is a common feature of Alzheimer’s disease and type 2 diabetes related to β-amyloid peptides (βA) and human amylin (hA), respectively. Both βA and hA form aggregates and fibrils and kill cultured cells. To investigate whether βA and hA display peptide-specific toxicity on cultured islet β-cells, we examined the effects of 1–40βA and 25–35βA peptides on hA-mediated cell death and [125I-Tyr37]hA precipitation. Synthetic hA aggregated in solution and evoked both conformation- and sequence-dependent cell death. While neither 1–40βA nor 25–35βA was toxic to islet β-cells, they suppressed hA-evoked cell death in a concentration-dependent and saturable manner. Only 1–40βA, but not 25–35βA, showed trophic effects on cultured islet β-cells and inhibited the precipitation of [125I]hA caused by hA. These results suggest that 25–35βA does not interfere with hA-mediated fibril formation. Suppression of hA-evoked death of cultured pancreatic islet β-cells by the βA peptides is likely to occur through a competing interaction at these cells.
Key words: β-Amyloid peptide, Amylin, Islet β-cell death, Aggregation.
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Received 12 June 2007/29 August 2007; accepted 22 December 2007doi:10.1016/j.cellbi.2007.12.016